Tovilović, Gordana

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Authority KeyName Variants
orcid::0000-0001-6150-3996
  • Tovilović, Gordana (12)
  • Tovilović-Kovačević, Gordana (2)
Projects
Synthesis and characterization of novel functional polymers and polymeric nanocomposites Sinteza i karakterizacija biološki aktivnih supstanci i kompjuterska simulacija bioloških sistema
Biomedicinska ispitivanja i razvoj nekih novih psihotropnih supstanci Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders
Structure-activity relationship of newly synthesized biological active compound Czech Science Foundation (No: 18-03932S).
The development of new synthetic methods and their application in the synthesis of natural products and biologically active molecules The role of autophagy in regulation of cancer cell death
Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM)
Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200168 (University of Belgrade, Faculty of Chemistry) Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200358 (BioSense Institute)
Ministry of Education, Science and Technological Development of the Republic of Serbia within Serbian-French Bilateral Project No. 337-00-8/2020-04 and the Ministry of Foreign Affairs of the Republic of France. UNESCO L'OREAL national scholarship program "For Women in Science" - 403F

Author's Bibliography

Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites

Pergal, Marija; Brkljačić, Jelena; Tovilović-Kovačević, Gordana; Špírková, Milena; Kodranov, Igor; Manojlović, Dragan; Ostojić, Sanja; Knežević, Nikola Ž.

(Elsevier, 2021)

TY  - JOUR
AU  - Pergal, Marija
AU  - Brkljačić, Jelena
AU  - Tovilović-Kovačević, Gordana
AU  - Špírková, Milena
AU  - Kodranov, Igor
AU  - Manojlović, Dragan
AU  - Ostojić, Sanja
AU  - Knežević, Nikola Ž.
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4016
AB  - Novel polyurethane nanocomposite (PUN) materials containing different surface-functionalized mesoporous silica nanoparticles (MSNs) were prepared by in situ polymerization methodology. Polyurethane network was formed from poly(dimethylsiloxane)-based macrodiol (PDMS), 4,4′-methylenediphenyldiisocyanate (MDI), and hyperbranched polyester of the second pseudo-generation (BH-20; used as crosslinking agent). PU and PU/MSN nanocomposites contained equal ratios of soft PDMS and hard MDI-BH-20 segments. Non-functionalized and surface-functionalized (with 3-(trihydroxysilyl)propyl methylphosphonate (FOMSN) and 2-[methoxy(polyethyleneoxy)6−9propyl]trimethoxysilane (PEGMSN)) MSNs were used as the nanofillers at a concentration of 1 wt%. Prepared materials were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), nanoindentation, equilibrium swelling and water absorption measurements. Characteristics of the prepared PUNs when in contact with a biological environment were assessed through testing their biocompatibility, protein adsorption and adhesion of endothelial cells. The favourable influence of MSNs on the physico-chemical and biological characteristics of these novel PUN materials was identified, which evidences their vast applicability potential as coatings for medical devices and implants.
PB  - Elsevier
T2  - Progress in Organic Coatings
T1  - Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites
VL  - 151
SP  - 106049
DO  - 10.1016/j.porgcoat.2020.106049
ER  - 
@article{
author = "Pergal, Marija and Brkljačić, Jelena and Tovilović-Kovačević, Gordana and Špírková, Milena and Kodranov, Igor and Manojlović, Dragan and Ostojić, Sanja and Knežević, Nikola Ž.",
year = "2021",
abstract = "Novel polyurethane nanocomposite (PUN) materials containing different surface-functionalized mesoporous silica nanoparticles (MSNs) were prepared by in situ polymerization methodology. Polyurethane network was formed from poly(dimethylsiloxane)-based macrodiol (PDMS), 4,4′-methylenediphenyldiisocyanate (MDI), and hyperbranched polyester of the second pseudo-generation (BH-20; used as crosslinking agent). PU and PU/MSN nanocomposites contained equal ratios of soft PDMS and hard MDI-BH-20 segments. Non-functionalized and surface-functionalized (with 3-(trihydroxysilyl)propyl methylphosphonate (FOMSN) and 2-[methoxy(polyethyleneoxy)6−9propyl]trimethoxysilane (PEGMSN)) MSNs were used as the nanofillers at a concentration of 1 wt%. Prepared materials were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), nanoindentation, equilibrium swelling and water absorption measurements. Characteristics of the prepared PUNs when in contact with a biological environment were assessed through testing their biocompatibility, protein adsorption and adhesion of endothelial cells. The favourable influence of MSNs on the physico-chemical and biological characteristics of these novel PUN materials was identified, which evidences their vast applicability potential as coatings for medical devices and implants.",
publisher = "Elsevier",
journal = "Progress in Organic Coatings",
title = "Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites",
volume = "151",
pages = "106049",
doi = "10.1016/j.porgcoat.2020.106049"
}
Pergal, M., Brkljačić, J., Tovilović-Kovačević, G., Špírková, M., Kodranov, I., Manojlović, D., Ostojić, S.,& Knežević, N. Ž.. (2021). Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites. in Progress in Organic Coatings
Elsevier., 151, 106049.
https://doi.org/10.1016/j.porgcoat.2020.106049
Pergal M, Brkljačić J, Tovilović-Kovačević G, Špírková M, Kodranov I, Manojlović D, Ostojić S, Knežević NŽ. Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites. in Progress in Organic Coatings. 2021;151:106049.
doi:10.1016/j.porgcoat.2020.106049 .
Pergal, Marija, Brkljačić, Jelena, Tovilović-Kovačević, Gordana, Špírková, Milena, Kodranov, Igor, Manojlović, Dragan, Ostojić, Sanja, Knežević, Nikola Ž., "Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites" in Progress in Organic Coatings, 151 (2021):106049,
https://doi.org/10.1016/j.porgcoat.2020.106049 . .
6
6

Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells

Stefanović, Ivan; Đonlagić, Jasna; Tovilović, Gordana; Nestorov, Jelena; Antić, Vesna; Ostojić, Sanja; Pergal, Marija

(Wiley-Blackwell, Hoboken, 2015)

TY  - JOUR
AU  - Stefanović, Ivan
AU  - Đonlagić, Jasna
AU  - Tovilović, Gordana
AU  - Nestorov, Jelena
AU  - Antić, Vesna
AU  - Ostojić, Sanja
AU  - Pergal, Marija
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1779
AB  - Polyurethane copolymers based on ,-dihydroxypropyl poly(dimethylsiloxane) (PDMS) with a range of soft segment contents were prepared by two-stage polymerization, and their microstructures, thermal, thermomechanical, and surface properties, as well as in vitro hemo- and cytocompatibility were evaluated. All utilized characterization methods confirmed the existence of moderately microphase separated structures with the appearance of some microphase mixing between segments as the PDMS (i.e., soft segment) content increased. Copolymers showed higher crystallinity, storage moduli, surface roughness, and surface free energy, but less hydrophobicity with decreasing PDMS content. Biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact, an extraction method and after pretreatment of copolymers with multicomponent protein mixture, as well as by a competitive protein adsorption assay. Copolymers showed no toxic effect to endothelial cells and all copolymers, except that with the lowest PDMS content, exhibited resistance to endothelial cell adhesion, suggesting their unsuitability for long-term biomedical devices which particularly require re-endothelialization. All copolymers exhibited excellent resistance to fibrinogen adsorption and adsorbed more albumin than fibrinogen in the competitive adsorption assay, suggesting their good hemocompatibility. The noncytotoxic chemistry of these synthesized materials, combined with their nonadherent properties which are inhospitable to cell attachment and growth, underlie the need for further investigations to clarify their potential for use in short-term biomedical devices.
PB  - Wiley-Blackwell, Hoboken
T2  - Journal of Biomedical Materials Research Part A
T1  - Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells
VL  - 103
IS  - 4
SP  - 1459
EP  - 1475
DO  - 10.1002/jbm.a.35285
ER  - 
@article{
author = "Stefanović, Ivan and Đonlagić, Jasna and Tovilović, Gordana and Nestorov, Jelena and Antić, Vesna and Ostojić, Sanja and Pergal, Marija",
year = "2015",
abstract = "Polyurethane copolymers based on ,-dihydroxypropyl poly(dimethylsiloxane) (PDMS) with a range of soft segment contents were prepared by two-stage polymerization, and their microstructures, thermal, thermomechanical, and surface properties, as well as in vitro hemo- and cytocompatibility were evaluated. All utilized characterization methods confirmed the existence of moderately microphase separated structures with the appearance of some microphase mixing between segments as the PDMS (i.e., soft segment) content increased. Copolymers showed higher crystallinity, storage moduli, surface roughness, and surface free energy, but less hydrophobicity with decreasing PDMS content. Biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact, an extraction method and after pretreatment of copolymers with multicomponent protein mixture, as well as by a competitive protein adsorption assay. Copolymers showed no toxic effect to endothelial cells and all copolymers, except that with the lowest PDMS content, exhibited resistance to endothelial cell adhesion, suggesting their unsuitability for long-term biomedical devices which particularly require re-endothelialization. All copolymers exhibited excellent resistance to fibrinogen adsorption and adsorbed more albumin than fibrinogen in the competitive adsorption assay, suggesting their good hemocompatibility. The noncytotoxic chemistry of these synthesized materials, combined with their nonadherent properties which are inhospitable to cell attachment and growth, underlie the need for further investigations to clarify their potential for use in short-term biomedical devices.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Biomedical Materials Research Part A",
title = "Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells",
volume = "103",
number = "4",
pages = "1459-1475",
doi = "10.1002/jbm.a.35285"
}
Stefanović, I., Đonlagić, J., Tovilović, G., Nestorov, J., Antić, V., Ostojić, S.,& Pergal, M.. (2015). Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells. in Journal of Biomedical Materials Research Part A
Wiley-Blackwell, Hoboken., 103(4), 1459-1475.
https://doi.org/10.1002/jbm.a.35285
Stefanović I, Đonlagić J, Tovilović G, Nestorov J, Antić V, Ostojić S, Pergal M. Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells. in Journal of Biomedical Materials Research Part A. 2015;103(4):1459-1475.
doi:10.1002/jbm.a.35285 .
Stefanović, Ivan, Đonlagić, Jasna, Tovilović, Gordana, Nestorov, Jelena, Antić, Vesna, Ostojić, Sanja, Pergal, Marija, "Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells" in Journal of Biomedical Materials Research Part A, 103, no. 4 (2015):1459-1475,
https://doi.org/10.1002/jbm.a.35285 . .
11
9
16

Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): Assessment of biocompatibility

Pergal, Marija; Nestorov, Jelena; Tovilović, Gordana; Ostojić, Sanja; Gođevac, Dejan; Vasiljević-Radović, Dana; Đonlagić, Jasna

(Wiley-Blackwell, Hoboken, 2014)

TY  - JOUR
AU  - Pergal, Marija
AU  - Nestorov, Jelena
AU  - Tovilović, Gordana
AU  - Ostojić, Sanja
AU  - Gođevac, Dejan
AU  - Vasiljević-Radović, Dana
AU  - Đonlagić, Jasna
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1398
AB  - Properties and biocompatibility of a series of thermoplastic poly(urethane-siloxane)s (TPUSs) based on alpha,omega-dihydroxy ethoxy propyl poly(dimethylsiloxane) (PDMS) for potential biomedical application were studied. Thin films of TPUSs with a different PDMS soft segment content were characterized by H-1 NMR, quantitative C-13 NMR, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), contact angle, and water absorption measurements. Different techniques (FTIR, AFM, and DMA) showed that decrease of PDMS content promotes microphase separation in TPUSs. Samples with a higher PDMS content have more hydrophobic surface and better waterproof performances, but lower degree of crystallinity. Biocompatibility of TPUSs was examined after attachment of endothelial cells to the untreated copolymer surface or surface pretreated with multicomponent protein mixture, and by using competitive protein adsorption assay. TPUSs did not exhibit any cytotoxicity toward endothelial cells, as measured by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assays. The untreated and proteins preadsorbed TPUS samples favored endothelial cells adhesion and growth, indicating good biocompatibility. All TPUSs adsorbed more albumin than fibrinogen in competitive protein adsorption experiment, which is feature regarded as beneficial for biocompatibility. The results indicate that TPUSs have good surface, thermo-mechanical, and biocompatible properties, which can be tailored for biomedical application requirements by adequate selection of the soft/hard segments ratio of the copolymers.
PB  - Wiley-Blackwell, Hoboken
T2  - Journal of Biomedical Materials Research Part A
T1  - Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): Assessment of biocompatibility
VL  - 102
IS  - 11
SP  - 3951
EP  - 3964
DO  - 10.1002/jbm.a.35071
ER  - 
@article{
author = "Pergal, Marija and Nestorov, Jelena and Tovilović, Gordana and Ostojić, Sanja and Gođevac, Dejan and Vasiljević-Radović, Dana and Đonlagić, Jasna",
year = "2014",
abstract = "Properties and biocompatibility of a series of thermoplastic poly(urethane-siloxane)s (TPUSs) based on alpha,omega-dihydroxy ethoxy propyl poly(dimethylsiloxane) (PDMS) for potential biomedical application were studied. Thin films of TPUSs with a different PDMS soft segment content were characterized by H-1 NMR, quantitative C-13 NMR, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), contact angle, and water absorption measurements. Different techniques (FTIR, AFM, and DMA) showed that decrease of PDMS content promotes microphase separation in TPUSs. Samples with a higher PDMS content have more hydrophobic surface and better waterproof performances, but lower degree of crystallinity. Biocompatibility of TPUSs was examined after attachment of endothelial cells to the untreated copolymer surface or surface pretreated with multicomponent protein mixture, and by using competitive protein adsorption assay. TPUSs did not exhibit any cytotoxicity toward endothelial cells, as measured by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assays. The untreated and proteins preadsorbed TPUS samples favored endothelial cells adhesion and growth, indicating good biocompatibility. All TPUSs adsorbed more albumin than fibrinogen in competitive protein adsorption experiment, which is feature regarded as beneficial for biocompatibility. The results indicate that TPUSs have good surface, thermo-mechanical, and biocompatible properties, which can be tailored for biomedical application requirements by adequate selection of the soft/hard segments ratio of the copolymers.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Biomedical Materials Research Part A",
title = "Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): Assessment of biocompatibility",
volume = "102",
number = "11",
pages = "3951-3964",
doi = "10.1002/jbm.a.35071"
}
Pergal, M., Nestorov, J., Tovilović, G., Ostojić, S., Gođevac, D., Vasiljević-Radović, D.,& Đonlagić, J.. (2014). Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): Assessment of biocompatibility. in Journal of Biomedical Materials Research Part A
Wiley-Blackwell, Hoboken., 102(11), 3951-3964.
https://doi.org/10.1002/jbm.a.35071
Pergal M, Nestorov J, Tovilović G, Ostojić S, Gođevac D, Vasiljević-Radović D, Đonlagić J. Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): Assessment of biocompatibility. in Journal of Biomedical Materials Research Part A. 2014;102(11):3951-3964.
doi:10.1002/jbm.a.35071 .
Pergal, Marija, Nestorov, Jelena, Tovilović, Gordana, Ostojić, Sanja, Gođevac, Dejan, Vasiljević-Radović, Dana, Đonlagić, Jasna, "Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): Assessment of biocompatibility" in Journal of Biomedical Materials Research Part A, 102, no. 11 (2014):3951-3964,
https://doi.org/10.1002/jbm.a.35071 . .
44
36
48

Surface characterization, hemo- and cytocompatibility of segmented poly(dimethylsiloxane)-based polyurethanes

Pergal, Marija; Nestorov, Jelena; Tovilović-Kovačević, Gordana; Jovančić, Petar; Pezo, Lato; Vasiljević-Radović, Dana; Đonlagić, Jasna

(Association of Chemical Engineers of Serbia, 2014)

TY  - JOUR
AU  - Pergal, Marija
AU  - Nestorov, Jelena
AU  - Tovilović-Kovačević, Gordana
AU  - Jovančić, Petar
AU  - Pezo, Lato
AU  - Vasiljević-Radović, Dana
AU  - Đonlagić, Jasna
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1456
AB  - Segmented polyurethanes based on poly(dimethylsiloxane), currently used for biomedical applications, have sub-optimal biocompatibility which reduces their efficacy. Improving the endothelial cell attachment and blood-contacting properties of PDMS-based copolymers would substantially improve their clinical applications. We have studied the surface properties and in vitro biocompatibility of two series of segmented poly(urethane-dimethylsiloxane)s (SPU-PDMS) based on hydroxypropyl- and hydroxyethoxypropyl-terminated PDMS with potential applications in blood-contacting medical devices. SPU-PDMS copolymers were characterized by contact angle measurements, surface free energy determination (calculated using the van Oss-Chaudhury-Good and Owens-Wendt methods), and atomic force microscopy. The biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact assay, before and after pre-treatment of copolymers with multicomponent protein mixture, as well as by a competitive blood-protein adsorption assay. The obtained results suggested good blood compatibility of synthesized copolymers. All copolymers exhibited good resistance to fibrinogen adsorption and all favored albumin adsorption. Copolymers based on hydroxyethoxypropyl-PDMS had lower hydrophobicity, higher surface free energy and better microphase separation in comparison with hydroxypropyl-PDMS-based copolymers, which promoted better endothelial cell attachment and growth on the surface of these polymers as compared to hydroxypropyl-PDMS-based copolymers. The results showed that SPU-PDMS copolymers display good surface properties, depending on the type of soft PDMS segments, which can be tailored for biomedical application requirements such as biomedical devices for short- and long-term uses.
AB  - Segmentirani poliuretani na bazi poli(dimetilsiloksana), koji se trenutno koriste u biomedicini, imaju biokompatibilnost ispod optimalne što smanjuje njihovu efikasnost. Poboljšavajući vezivanje endotelnih ćelija i svojstva kopolimera na bazi PDMS u dodiru sa krvlju značajno bi se poboljšala i proširila njihova klinička primena. U ovom radu su proučavana površinska svojstva i in vitro biokompatibilnost dve serije segmentiranih poli(uretan-dimetilsiloksana) (SPU-PDMS) na bazi hidroksipropil- i hidroksietoksipropil- PDMS pretpolimera sa potencijalnim primenama u medicinskim uredjajima u kontaktu sa krvlju. SPU-PDMS kopolimeri su karakterisani merenjem kontaktnih uglova, određivanjem površinske energije (izračunate prema van Oss-Chaudhury-Good i Owens-Wendt metodama), i mikroskopijom atomskih sila. Biokompatibilnost kopolimera je ispitivana primenom endotelnih EA.hy926 ćelija u direktnom kontaktu, pre i nakon pretretiranja kopolimera sa višekomponentnom smešom proteina, kao i pomoću kompetitivne adsorpcije proteina. Dobijeni rezultati su potvrdili da sintetisani kopolimeri imaju dobru kompatibilnost prema krvi. Svi sintetisani kopolimeri pokazivali su dobru otpornost prema adsorpciji fibrinogena i svi kopolimeri su favorizovali adsorpciju albumina. Kopolimeri na bazi hidroksietoksipropil-PDMS imali su manju hidrofobnost, veću površinsku energiju, i bolju mikrofaznu separaciju u poređenju sa kopolimerima na bazi hidroksipropil-PDMS, što je dovelo do boljeg vezivanja i rasta endotelnih ćelija na površini ovih polimera u poređenju sa kopolimerima na bazi hidroksipropil-PDMS. Rezultati su pokazali da SPU-PDMS kopolimeri prikazuju dobra površinska svojstva, zavisno od vrste mekih PDMS segmenata, koja se mogu prilagođavati zahtevima u biomedicini, kao što su biomedicinski uređaji za kratkoročnu i dugoročnu upotrebu.
PB  - Association of Chemical Engineers of Serbia
T2  - Hemijska industrija
T1  - Surface characterization, hemo- and cytocompatibility of segmented poly(dimethylsiloxane)-based polyurethanes
T1  - Površinska karakterizacija, hemo- i citokompatibilnost segmentiranih poliuretana na bazi poli(dimetilsiloksana)
VL  - 68
IS  - 6
SP  - 731
EP  - 741
DO  - 10.2298/HEMIND141103082P
ER  - 
@article{
author = "Pergal, Marija and Nestorov, Jelena and Tovilović-Kovačević, Gordana and Jovančić, Petar and Pezo, Lato and Vasiljević-Radović, Dana and Đonlagić, Jasna",
year = "2014",
abstract = "Segmented polyurethanes based on poly(dimethylsiloxane), currently used for biomedical applications, have sub-optimal biocompatibility which reduces their efficacy. Improving the endothelial cell attachment and blood-contacting properties of PDMS-based copolymers would substantially improve their clinical applications. We have studied the surface properties and in vitro biocompatibility of two series of segmented poly(urethane-dimethylsiloxane)s (SPU-PDMS) based on hydroxypropyl- and hydroxyethoxypropyl-terminated PDMS with potential applications in blood-contacting medical devices. SPU-PDMS copolymers were characterized by contact angle measurements, surface free energy determination (calculated using the van Oss-Chaudhury-Good and Owens-Wendt methods), and atomic force microscopy. The biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact assay, before and after pre-treatment of copolymers with multicomponent protein mixture, as well as by a competitive blood-protein adsorption assay. The obtained results suggested good blood compatibility of synthesized copolymers. All copolymers exhibited good resistance to fibrinogen adsorption and all favored albumin adsorption. Copolymers based on hydroxyethoxypropyl-PDMS had lower hydrophobicity, higher surface free energy and better microphase separation in comparison with hydroxypropyl-PDMS-based copolymers, which promoted better endothelial cell attachment and growth on the surface of these polymers as compared to hydroxypropyl-PDMS-based copolymers. The results showed that SPU-PDMS copolymers display good surface properties, depending on the type of soft PDMS segments, which can be tailored for biomedical application requirements such as biomedical devices for short- and long-term uses., Segmentirani poliuretani na bazi poli(dimetilsiloksana), koji se trenutno koriste u biomedicini, imaju biokompatibilnost ispod optimalne što smanjuje njihovu efikasnost. Poboljšavajući vezivanje endotelnih ćelija i svojstva kopolimera na bazi PDMS u dodiru sa krvlju značajno bi se poboljšala i proširila njihova klinička primena. U ovom radu su proučavana površinska svojstva i in vitro biokompatibilnost dve serije segmentiranih poli(uretan-dimetilsiloksana) (SPU-PDMS) na bazi hidroksipropil- i hidroksietoksipropil- PDMS pretpolimera sa potencijalnim primenama u medicinskim uredjajima u kontaktu sa krvlju. SPU-PDMS kopolimeri su karakterisani merenjem kontaktnih uglova, određivanjem površinske energije (izračunate prema van Oss-Chaudhury-Good i Owens-Wendt metodama), i mikroskopijom atomskih sila. Biokompatibilnost kopolimera je ispitivana primenom endotelnih EA.hy926 ćelija u direktnom kontaktu, pre i nakon pretretiranja kopolimera sa višekomponentnom smešom proteina, kao i pomoću kompetitivne adsorpcije proteina. Dobijeni rezultati su potvrdili da sintetisani kopolimeri imaju dobru kompatibilnost prema krvi. Svi sintetisani kopolimeri pokazivali su dobru otpornost prema adsorpciji fibrinogena i svi kopolimeri su favorizovali adsorpciju albumina. Kopolimeri na bazi hidroksietoksipropil-PDMS imali su manju hidrofobnost, veću površinsku energiju, i bolju mikrofaznu separaciju u poređenju sa kopolimerima na bazi hidroksipropil-PDMS, što je dovelo do boljeg vezivanja i rasta endotelnih ćelija na površini ovih polimera u poređenju sa kopolimerima na bazi hidroksipropil-PDMS. Rezultati su pokazali da SPU-PDMS kopolimeri prikazuju dobra površinska svojstva, zavisno od vrste mekih PDMS segmenata, koja se mogu prilagođavati zahtevima u biomedicini, kao što su biomedicinski uređaji za kratkoročnu i dugoročnu upotrebu.",
publisher = "Association of Chemical Engineers of Serbia",
journal = "Hemijska industrija",
title = "Surface characterization, hemo- and cytocompatibility of segmented poly(dimethylsiloxane)-based polyurethanes, Površinska karakterizacija, hemo- i citokompatibilnost segmentiranih poliuretana na bazi poli(dimetilsiloksana)",
volume = "68",
number = "6",
pages = "731-741",
doi = "10.2298/HEMIND141103082P"
}
Pergal, M., Nestorov, J., Tovilović-Kovačević, G., Jovančić, P., Pezo, L., Vasiljević-Radović, D.,& Đonlagić, J.. (2014). Surface characterization, hemo- and cytocompatibility of segmented poly(dimethylsiloxane)-based polyurethanes. in Hemijska industrija
Association of Chemical Engineers of Serbia., 68(6), 731-741.
https://doi.org/10.2298/HEMIND141103082P
Pergal M, Nestorov J, Tovilović-Kovačević G, Jovančić P, Pezo L, Vasiljević-Radović D, Đonlagić J. Surface characterization, hemo- and cytocompatibility of segmented poly(dimethylsiloxane)-based polyurethanes. in Hemijska industrija. 2014;68(6):731-741.
doi:10.2298/HEMIND141103082P .
Pergal, Marija, Nestorov, Jelena, Tovilović-Kovačević, Gordana, Jovančić, Petar, Pezo, Lato, Vasiljević-Radović, Dana, Đonlagić, Jasna, "Surface characterization, hemo- and cytocompatibility of segmented poly(dimethylsiloxane)-based polyurethanes" in Hemijska industrija, 68, no. 6 (2014):731-741,
https://doi.org/10.2298/HEMIND141103082P . .
4
2
6

N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling

Šukalović, Vladimir; Bogdan, Anca Elena; Tovilović, Gordana; Ignjatović, Đurđica S.; Andrić, Deana; Kostić Rajačić, Slađana; Šoškić, Vukić

(Wiley-V C H Verlag Gmbh, Weinheim, 2013)

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Bogdan, Anca Elena
AU  - Tovilović, Gordana
AU  - Ignjatović, Đurđica S.
AU  - Andrić, Deana
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1193
AB  - The ratio of affinities toward the dopamine D-2 and the 5-hydroxytryptamine 5-HT1A receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para-N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure-activity relationship studies on dopamine D-2 and 5-hydroxytryptamine 5-HT1A receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor-ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D-2/5-HT1A profile.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Archiv der Pharmazie
T1  - N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling
VL  - 346
IS  - 10
SP  - 708
EP  - 717
DO  - 10.1002/ardp.201300189
ER  - 
@article{
author = "Šukalović, Vladimir and Bogdan, Anca Elena and Tovilović, Gordana and Ignjatović, Đurđica S. and Andrić, Deana and Kostić Rajačić, Slađana and Šoškić, Vukić",
year = "2013",
abstract = "The ratio of affinities toward the dopamine D-2 and the 5-hydroxytryptamine 5-HT1A receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para-N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure-activity relationship studies on dopamine D-2 and 5-hydroxytryptamine 5-HT1A receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor-ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D-2/5-HT1A profile.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Archiv der Pharmazie",
title = "N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling",
volume = "346",
number = "10",
pages = "708-717",
doi = "10.1002/ardp.201300189"
}
Šukalović, V., Bogdan, A. E., Tovilović, G., Ignjatović, Đ. S., Andrić, D., Kostić Rajačić, S.,& Šoškić, V.. (2013). N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling. in Archiv der Pharmazie
Wiley-V C H Verlag Gmbh, Weinheim., 346(10), 708-717.
https://doi.org/10.1002/ardp.201300189
Šukalović V, Bogdan AE, Tovilović G, Ignjatović ĐS, Andrić D, Kostić Rajačić S, Šoškić V. N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling. in Archiv der Pharmazie. 2013;346(10):708-717.
doi:10.1002/ardp.201300189 .
Šukalović, Vladimir, Bogdan, Anca Elena, Tovilović, Gordana, Ignjatović, Đurđica S., Andrić, Deana, Kostić Rajačić, Slađana, Šoškić, Vukić, "N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling" in Archiv der Pharmazie, 346, no. 10 (2013):708-717,
https://doi.org/10.1002/ardp.201300189 . .
5
5
6

Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death

Tovilović, Gordana; Zogovic, Nevena; Šoškić, Vukić; Schrattenholz, Andre; Kostić Rajačić, Slađana; Misirkić-Marjanović, Maja; Janjetovic, Kristina; Vucicevic, Ljubica; Arsikin, Katarina; Harhaji-Trajković, Ljubica; Trajković, Vladimir

(Oxford : Pergamon-Elsevier Science Ltd, 2013)

TY  - JOUR
AU  - Tovilović, Gordana
AU  - Zogovic, Nevena
AU  - Šoškić, Vukić
AU  - Schrattenholz, Andre
AU  - Kostić Rajačić, Slađana
AU  - Misirkić-Marjanović, Maja
AU  - Janjetovic, Kristina
AU  - Vucicevic, Ljubica
AU  - Arsikin, Katarina
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1201
AB  - We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SH-SY5Y neuroblastoma cells from the neurotoxin 6-hydroxydopamine (6-OHDA). The compound with the most potent neuroprotective action was N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), which reduced 6-OHDA-induced apoptotic death through stabilization of mitochondrial membrane and subsequent prevention of superoxide production, caspase activation and DNA fragmentation. 6-OHDA-triggered autophagic response was also reduced by 6b, which prevented inactivation of the main autophagy repressor mTOR, upregulation of proautophagic beclin-1, conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to autophagosome-associAed LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3 beta gene silencing or pharmacological autophagy blockers 3-methyladenine or bafilomycin A1, mimicked the cytoprotective effect of 6b. While the treatment with 6b had no effect on the phosphorylation of proapoptotic MAP kinases ERR and JNK, it markedly increased the phosphorylation of the prosurvival kinase Akt in 6-OHDA-treated cells. Akt inhibitor DEBC or RNA interference-mediated Akt silencing reduced the ability of 6b to block 6-0HDA-triggered apoptotic and autophagic responses, thus confirming their dependency on Akt activation. The cytoprotective effect of 6b was also observed in 6-OHDA-treated neuronal PC12 cells, but not in SH-SY5Y or PC12 cells exposed to 1-methyl-4-phenylpyridinium, indicating that the observed neuroprotection was dependent on the cytotoxic stimulus. Because of the ability to prevent 6-OHDA induced apoptotic/autophagic cell death through activation of Akt, the investigated arylpiperazines could be potential candidates for treatment of neurodegenerative diseases.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Neuropharmacology
T1  - Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death
VL  - 72
SP  - 224
EP  - 235
DO  - 10.1016/j.neuropharm.2013.04.037
ER  - 
@article{
author = "Tovilović, Gordana and Zogovic, Nevena and Šoškić, Vukić and Schrattenholz, Andre and Kostić Rajačić, Slađana and Misirkić-Marjanović, Maja and Janjetovic, Kristina and Vucicevic, Ljubica and Arsikin, Katarina and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2013",
abstract = "We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SH-SY5Y neuroblastoma cells from the neurotoxin 6-hydroxydopamine (6-OHDA). The compound with the most potent neuroprotective action was N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), which reduced 6-OHDA-induced apoptotic death through stabilization of mitochondrial membrane and subsequent prevention of superoxide production, caspase activation and DNA fragmentation. 6-OHDA-triggered autophagic response was also reduced by 6b, which prevented inactivation of the main autophagy repressor mTOR, upregulation of proautophagic beclin-1, conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to autophagosome-associAed LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3 beta gene silencing or pharmacological autophagy blockers 3-methyladenine or bafilomycin A1, mimicked the cytoprotective effect of 6b. While the treatment with 6b had no effect on the phosphorylation of proapoptotic MAP kinases ERR and JNK, it markedly increased the phosphorylation of the prosurvival kinase Akt in 6-OHDA-treated cells. Akt inhibitor DEBC or RNA interference-mediated Akt silencing reduced the ability of 6b to block 6-0HDA-triggered apoptotic and autophagic responses, thus confirming their dependency on Akt activation. The cytoprotective effect of 6b was also observed in 6-OHDA-treated neuronal PC12 cells, but not in SH-SY5Y or PC12 cells exposed to 1-methyl-4-phenylpyridinium, indicating that the observed neuroprotection was dependent on the cytotoxic stimulus. Because of the ability to prevent 6-OHDA induced apoptotic/autophagic cell death through activation of Akt, the investigated arylpiperazines could be potential candidates for treatment of neurodegenerative diseases.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Neuropharmacology",
title = "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death",
volume = "72",
pages = "224-235",
doi = "10.1016/j.neuropharm.2013.04.037"
}
Tovilović, G., Zogovic, N., Šoškić, V., Schrattenholz, A., Kostić Rajačić, S., Misirkić-Marjanović, M., Janjetovic, K., Vucicevic, L., Arsikin, K., Harhaji-Trajković, L.,& Trajković, V.. (2013). Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death. in Neuropharmacology
Oxford : Pergamon-Elsevier Science Ltd., 72, 224-235.
https://doi.org/10.1016/j.neuropharm.2013.04.037
Tovilović G, Zogovic N, Šoškić V, Schrattenholz A, Kostić Rajačić S, Misirkić-Marjanović M, Janjetovic K, Vucicevic L, Arsikin K, Harhaji-Trajković L, Trajković V. Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death. in Neuropharmacology. 2013;72:224-235.
doi:10.1016/j.neuropharm.2013.04.037 .
Tovilović, Gordana, Zogovic, Nevena, Šoškić, Vukić, Schrattenholz, Andre, Kostić Rajačić, Slađana, Misirkić-Marjanović, Maja, Janjetovic, Kristina, Vucicevic, Ljubica, Arsikin, Katarina, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death" in Neuropharmacology, 72 (2013):224-235,
https://doi.org/10.1016/j.neuropharm.2013.04.037 . .
17
17
18

In Vitro Biocompatibility Evaluation of Novel Urethane-Siloxane Co-Polymers Based on Poly(epsilon-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(epsilon-Caprolactone)

Pergal, Marija; Antić, Vesna; Tovilović, Gordana; Nestorov, Jelena; Vasiljević-Radović, Dana; Đonlagić, Jasna

(Taylor & Francis Ltd, Abingdon, 2012)

TY  - JOUR
AU  - Pergal, Marija
AU  - Antić, Vesna
AU  - Tovilović, Gordana
AU  - Nestorov, Jelena
AU  - Vasiljević-Radović, Dana
AU  - Đonlagić, Jasna
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1110
AB  - Novel polyurethane co-polymers (TPUs), based on poly(epsilon-caprolactone)-block-poly(dimethylsiloxane)-block-poly(epsilon-caprolactone) (PCL-PDMS-PCL) as soft segment and 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD) as hard segment, were synthesized and evaluated for biomedical applications. The content of hard segments (HS) in the polymer chains was varied from 9 to 63 wt%. The influence of the content and length of the HS on the thermal, surface, mechanical properties and biocompatibility was investigated. The structure, composition and HS length were examined using H-1- and quantitative C-13-NMR spectroscopy. DSC results implied that the synthesized TPUs were semicrystalline polymers in which both the hard MDI/BD and soft PCL-PDMS-PCL segments participated. It was found that an increase in the average HS length (from 1.2 to 14.4 MDI/BD units) was accompanied by an increase in the crystallinity of the hard segments, storage moduli, hydrophilicity and degree of microphase separation of the co-polymers. Depending on the HS content, a gradual variation in surface properties of co-polymers was revealed by FTIR, AFM and static water contact angle measurements. The in vitro biocompatibility of co-polymers was evaluated using the endothelial EA. hy926 cell line and protein adsorption on the polyurethane films. All synthesized TPUs adsorbed more albumin than fibrinogen from multicomponent protein mixture, which may indicate biocompatibility. The polyurethane films with high HS content and/or high roughness coefficient exhibit good surface properties and biocompatible behavior, which was confirmed by non-toxic effects to cells and good cell adhesion. Therefore, the non-cytotoxic chemistry of the co-polymers makes them good candidates for further development as biomedical implants.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Journal of Biomaterials Science-Polymer Edition
T1  - In Vitro Biocompatibility Evaluation of Novel Urethane-Siloxane Co-Polymers Based on Poly(epsilon-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(epsilon-Caprolactone)
VL  - 23
IS  - 13
SP  - 1629
EP  - 1657
DO  - 10.1163/092050611X589338
ER  - 
@article{
author = "Pergal, Marija and Antić, Vesna and Tovilović, Gordana and Nestorov, Jelena and Vasiljević-Radović, Dana and Đonlagić, Jasna",
year = "2012",
abstract = "Novel polyurethane co-polymers (TPUs), based on poly(epsilon-caprolactone)-block-poly(dimethylsiloxane)-block-poly(epsilon-caprolactone) (PCL-PDMS-PCL) as soft segment and 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD) as hard segment, were synthesized and evaluated for biomedical applications. The content of hard segments (HS) in the polymer chains was varied from 9 to 63 wt%. The influence of the content and length of the HS on the thermal, surface, mechanical properties and biocompatibility was investigated. The structure, composition and HS length were examined using H-1- and quantitative C-13-NMR spectroscopy. DSC results implied that the synthesized TPUs were semicrystalline polymers in which both the hard MDI/BD and soft PCL-PDMS-PCL segments participated. It was found that an increase in the average HS length (from 1.2 to 14.4 MDI/BD units) was accompanied by an increase in the crystallinity of the hard segments, storage moduli, hydrophilicity and degree of microphase separation of the co-polymers. Depending on the HS content, a gradual variation in surface properties of co-polymers was revealed by FTIR, AFM and static water contact angle measurements. The in vitro biocompatibility of co-polymers was evaluated using the endothelial EA. hy926 cell line and protein adsorption on the polyurethane films. All synthesized TPUs adsorbed more albumin than fibrinogen from multicomponent protein mixture, which may indicate biocompatibility. The polyurethane films with high HS content and/or high roughness coefficient exhibit good surface properties and biocompatible behavior, which was confirmed by non-toxic effects to cells and good cell adhesion. Therefore, the non-cytotoxic chemistry of the co-polymers makes them good candidates for further development as biomedical implants.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Journal of Biomaterials Science-Polymer Edition",
title = "In Vitro Biocompatibility Evaluation of Novel Urethane-Siloxane Co-Polymers Based on Poly(epsilon-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(epsilon-Caprolactone)",
volume = "23",
number = "13",
pages = "1629-1657",
doi = "10.1163/092050611X589338"
}
Pergal, M., Antić, V., Tovilović, G., Nestorov, J., Vasiljević-Radović, D.,& Đonlagić, J.. (2012). In Vitro Biocompatibility Evaluation of Novel Urethane-Siloxane Co-Polymers Based on Poly(epsilon-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(epsilon-Caprolactone). in Journal of Biomaterials Science-Polymer Edition
Taylor & Francis Ltd, Abingdon., 23(13), 1629-1657.
https://doi.org/10.1163/092050611X589338
Pergal M, Antić V, Tovilović G, Nestorov J, Vasiljević-Radović D, Đonlagić J. In Vitro Biocompatibility Evaluation of Novel Urethane-Siloxane Co-Polymers Based on Poly(epsilon-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(epsilon-Caprolactone). in Journal of Biomaterials Science-Polymer Edition. 2012;23(13):1629-1657.
doi:10.1163/092050611X589338 .
Pergal, Marija, Antić, Vesna, Tovilović, Gordana, Nestorov, Jelena, Vasiljević-Radović, Dana, Đonlagić, Jasna, "In Vitro Biocompatibility Evaluation of Novel Urethane-Siloxane Co-Polymers Based on Poly(epsilon-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(epsilon-Caprolactone)" in Journal of Biomaterials Science-Polymer Edition, 23, no. 13 (2012):1629-1657,
https://doi.org/10.1163/092050611X589338 . .
27
31
39

Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors

Šukalović, Vladimir; Ignjatović, Đurđica S.; Tovilović, Gordana; Andrić, Deana; Shakib, Kaveh; Kostić Rajačić, Slađana; Šoškić, Vukić

(Oxford : Pergamon-Elsevier Science Ltd, 2012)

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Ignjatović, Đurđica S.
AU  - Tovilović, Gordana
AU  - Andrić, Deana
AU  - Shakib, Kaveh
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/974
AB  - It is suggested that the ratio of dopamine D-2 to 5-hydroxytryptamine 5-HT1A activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D-2 and 5-hydrohytryptamine 5-HT1A receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT1A receptors.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors
VL  - 22
IS  - 12
SP  - 3967
EP  - 3972
DO  - 10.1016/j.bmcl.2012.04.098
ER  - 
@article{
author = "Šukalović, Vladimir and Ignjatović, Đurđica S. and Tovilović, Gordana and Andrić, Deana and Shakib, Kaveh and Kostić Rajačić, Slađana and Šoškić, Vukić",
year = "2012",
abstract = "It is suggested that the ratio of dopamine D-2 to 5-hydroxytryptamine 5-HT1A activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D-2 and 5-hydrohytryptamine 5-HT1A receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT1A receptors.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors",
volume = "22",
number = "12",
pages = "3967-3972",
doi = "10.1016/j.bmcl.2012.04.098"
}
Šukalović, V., Ignjatović, Đ. S., Tovilović, G., Andrić, D., Shakib, K., Kostić Rajačić, S.,& Šoškić, V.. (2012). Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors. in Bioorganic and Medicinal Chemistry Letters
Oxford : Pergamon-Elsevier Science Ltd., 22(12), 3967-3972.
https://doi.org/10.1016/j.bmcl.2012.04.098
Šukalović V, Ignjatović ĐS, Tovilović G, Andrić D, Shakib K, Kostić Rajačić S, Šoškić V. Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors. in Bioorganic and Medicinal Chemistry Letters. 2012;22(12):3967-3972.
doi:10.1016/j.bmcl.2012.04.098 .
Šukalović, Vladimir, Ignjatović, Đurđica S., Tovilović, Gordana, Andrić, Deana, Shakib, Kaveh, Kostić Rajačić, Slađana, Šoškić, Vukić, "Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors" in Bioorganic and Medicinal Chemistry Letters, 22, no. 12 (2012):3967-3972,
https://doi.org/10.1016/j.bmcl.2012.04.098 . .
7
9
11

Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis

Tovilović, Gordana; Zogovic, Nevena; Harhaji-Trajković, Ljubica; Misirkić-Marjanović, Maja; Janjetovic, Kristina; Vucicevic, Ljubica; Kostić Rajačić, Slađana; Schrattenholz, Andre; Isaković, Aleksandra; Šoškić, Vukić; Trajković, Vladimir

(Wiley-V C H Verlag Gmbh, Weinheim, 2012)

TY  - JOUR
AU  - Tovilović, Gordana
AU  - Zogovic, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Misirkić-Marjanović, Maja
AU  - Janjetovic, Kristina
AU  - Vucicevic, Ljubica
AU  - Kostić Rajačić, Slađana
AU  - Schrattenholz, Andre
AU  - Isaković, Aleksandra
AU  - Šoškić, Vukić
AU  - Trajković, Vladimir
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1037
AB  - The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D1/D2 receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Chemmedchem
T1  - Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis
VL  - 7
IS  - 3
SP  - 495
EP  - 508
DO  - 10.1002/cmdc.201100537
ER  - 
@article{
author = "Tovilović, Gordana and Zogovic, Nevena and Harhaji-Trajković, Ljubica and Misirkić-Marjanović, Maja and Janjetovic, Kristina and Vucicevic, Ljubica and Kostić Rajačić, Slađana and Schrattenholz, Andre and Isaković, Aleksandra and Šoškić, Vukić and Trajković, Vladimir",
year = "2012",
abstract = "The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D1/D2 receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Chemmedchem",
title = "Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis",
volume = "7",
number = "3",
pages = "495-508",
doi = "10.1002/cmdc.201100537"
}
Tovilović, G., Zogovic, N., Harhaji-Trajković, L., Misirkić-Marjanović, M., Janjetovic, K., Vucicevic, L., Kostić Rajačić, S., Schrattenholz, A., Isaković, A., Šoškić, V.,& Trajković, V.. (2012). Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis. in Chemmedchem
Wiley-V C H Verlag Gmbh, Weinheim., 7(3), 495-508.
https://doi.org/10.1002/cmdc.201100537
Tovilović G, Zogovic N, Harhaji-Trajković L, Misirkić-Marjanović M, Janjetovic K, Vucicevic L, Kostić Rajačić S, Schrattenholz A, Isaković A, Šoškić V, Trajković V. Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis. in Chemmedchem. 2012;7(3):495-508.
doi:10.1002/cmdc.201100537 .
Tovilović, Gordana, Zogovic, Nevena, Harhaji-Trajković, Ljubica, Misirkić-Marjanović, Maja, Janjetovic, Kristina, Vucicevic, Ljubica, Kostić Rajačić, Slađana, Schrattenholz, Andre, Isaković, Aleksandra, Šoškić, Vukić, Trajković, Vladimir, "Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis" in Chemmedchem, 7, no. 3 (2012):495-508,
https://doi.org/10.1002/cmdc.201100537 . .
8
9
8

A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids

Trmcic, Milena V.; Matović, Radomir; Tovilović, Gordana; Ristic, Biljana Z.; Trajković, Vladimir; Ferjančić, Zorana; Saičić, Radomir N.

(Royal Soc Chemistry, Cambridge, 2012)

TY  - JOUR
AU  - Trmcic, Milena V.
AU  - Matović, Radomir
AU  - Tovilović, Gordana
AU  - Ristic, Biljana Z.
AU  - Trajković, Vladimir
AU  - Ferjančić, Zorana
AU  - Saičić, Radomir N.
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/981
AB  - The design, synthesis and biological evaluation of a novel C, D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic & Biomolecular Chemistry
T1  - A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids
VL  - 10
IS  - 25
SP  - 4933
EP  - 4942
DO  - 10.1039/c2ob25514f
ER  - 
@article{
author = "Trmcic, Milena V. and Matović, Radomir and Tovilović, Gordana and Ristic, Biljana Z. and Trajković, Vladimir and Ferjančić, Zorana and Saičić, Radomir N.",
year = "2012",
abstract = "The design, synthesis and biological evaluation of a novel C, D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic & Biomolecular Chemistry",
title = "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids",
volume = "10",
number = "25",
pages = "4933-4942",
doi = "10.1039/c2ob25514f"
}
Trmcic, M. V., Matović, R., Tovilović, G., Ristic, B. Z., Trajković, V., Ferjančić, Z.,& Saičić, R. N.. (2012). A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids. in Organic & Biomolecular Chemistry
Royal Soc Chemistry, Cambridge., 10(25), 4933-4942.
https://doi.org/10.1039/c2ob25514f
Trmcic MV, Matović R, Tovilović G, Ristic BZ, Trajković V, Ferjančić Z, Saičić RN. A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids. in Organic & Biomolecular Chemistry. 2012;10(25):4933-4942.
doi:10.1039/c2ob25514f .
Trmcic, Milena V., Matović, Radomir, Tovilović, Gordana, Ristic, Biljana Z., Trajković, Vladimir, Ferjančić, Zorana, Saičić, Radomir N., "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids" in Organic & Biomolecular Chemistry, 10, no. 25 (2012):4933-4942,
https://doi.org/10.1039/c2ob25514f . .
12
12
14

Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands

Tomić, Mirko; Vasković, Djurdjica; Tovilović, Gordana; Andrić, Deana; Penjišević, Jelena; Kostić Rajačić, Slađana

(Wiley-Blackwell, Malden, 2011)

TY  - JOUR
AU  - Tomić, Mirko
AU  - Vasković, Djurdjica
AU  - Tovilović, Gordana
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Kostić Rajačić, Slađana
PY  - 2011
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/916
AB  - Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D-2, 5-HT2A, and alpha(1)-adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with brominemay greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT2A/D-2 pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl) phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency.
PB  - Wiley-Blackwell, Malden
T2  - Archiv der Pharmazie
T1  - Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands
VL  - 344
IS  - 5
SP  - 287
EP  - 291
DO  - 10.1002/ardp.200900168
ER  - 
@article{
author = "Tomić, Mirko and Vasković, Djurdjica and Tovilović, Gordana and Andrić, Deana and Penjišević, Jelena and Kostić Rajačić, Slađana",
year = "2011",
abstract = "Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D-2, 5-HT2A, and alpha(1)-adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with brominemay greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT2A/D-2 pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl) phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency.",
publisher = "Wiley-Blackwell, Malden",
journal = "Archiv der Pharmazie",
title = "Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands",
volume = "344",
number = "5",
pages = "287-291",
doi = "10.1002/ardp.200900168"
}
Tomić, M., Vasković, D., Tovilović, G., Andrić, D., Penjišević, J.,& Kostić Rajačić, S.. (2011). Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands. in Archiv der Pharmazie
Wiley-Blackwell, Malden., 344(5), 287-291.
https://doi.org/10.1002/ardp.200900168
Tomić M, Vasković D, Tovilović G, Andrić D, Penjišević J, Kostić Rajačić S. Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands. in Archiv der Pharmazie. 2011;344(5):287-291.
doi:10.1002/ardp.200900168 .
Tomić, Mirko, Vasković, Djurdjica, Tovilović, Gordana, Andrić, Deana, Penjišević, Jelena, Kostić Rajačić, Slađana, "Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands" in Archiv der Pharmazie, 344, no. 5 (2011):287-291,
https://doi.org/10.1002/ardp.200900168 . .
4
4
5

Two new phenylpiperazines with atypical antipsychotic potential

Tomić, Mirko; Ignjatović, D.; Tovilović, Gordana; Andrić, Deana; Roglić, Goran; Kostić Rajačić, Slađana

(Oxford : Pergamon-Elsevier Science Ltd, 2007)

TY  - JOUR
AU  - Tomić, Mirko
AU  - Ignjatović, D.
AU  - Tovilović, Gordana
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
PY  - 2007
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/354
AB  - Two new series of substituted arylpiperazines with heterocyclic 3-propoxy-benzimidazole or 3-propoxy-benzimidazole-2-thione groups were synthesized and their in vitro binding affinities for the D2, 5-HT1A, 5-HT2A, and α1-adrenergic receptors determined. Among them, only two compounds with phenyl aryl-constituent (8a and 9a) showed 5-HT2A/D2 pKi binding ratios proposed for atypical neuroleptics. As to their behavioral screening on rodents, both compounds exhibited a non-cataleptic action in rats and antagonized d-amphetamine-induced hyperlocomotion in mice, suggesting their possible atypical antipsychotic potency.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - Two new phenylpiperazines with atypical antipsychotic potential
VL  - 17
IS  - 21
SP  - 5749
EP  - 5753
DO  - 10.1016/j.bmcl.2007.08.066
ER  - 
@article{
author = "Tomić, Mirko and Ignjatović, D. and Tovilović, Gordana and Andrić, Deana and Roglić, Goran and Kostić Rajačić, Slađana",
year = "2007",
abstract = "Two new series of substituted arylpiperazines with heterocyclic 3-propoxy-benzimidazole or 3-propoxy-benzimidazole-2-thione groups were synthesized and their in vitro binding affinities for the D2, 5-HT1A, 5-HT2A, and α1-adrenergic receptors determined. Among them, only two compounds with phenyl aryl-constituent (8a and 9a) showed 5-HT2A/D2 pKi binding ratios proposed for atypical neuroleptics. As to their behavioral screening on rodents, both compounds exhibited a non-cataleptic action in rats and antagonized d-amphetamine-induced hyperlocomotion in mice, suggesting their possible atypical antipsychotic potency.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "Two new phenylpiperazines with atypical antipsychotic potential",
volume = "17",
number = "21",
pages = "5749-5753",
doi = "10.1016/j.bmcl.2007.08.066"
}
Tomić, M., Ignjatović, D., Tovilović, G., Andrić, D., Roglić, G.,& Kostić Rajačić, S.. (2007). Two new phenylpiperazines with atypical antipsychotic potential. in Bioorganic and Medicinal Chemistry Letters
Oxford : Pergamon-Elsevier Science Ltd., 17(21), 5749-5753.
https://doi.org/10.1016/j.bmcl.2007.08.066
Tomić M, Ignjatović D, Tovilović G, Andrić D, Roglić G, Kostić Rajačić S. Two new phenylpiperazines with atypical antipsychotic potential. in Bioorganic and Medicinal Chemistry Letters. 2007;17(21):5749-5753.
doi:10.1016/j.bmcl.2007.08.066 .
Tomić, Mirko, Ignjatović, D., Tovilović, Gordana, Andrić, Deana, Roglić, Goran, Kostić Rajačić, Slađana, "Two new phenylpiperazines with atypical antipsychotic potential" in Bioorganic and Medicinal Chemistry Letters, 17, no. 21 (2007):5749-5753,
https://doi.org/10.1016/j.bmcl.2007.08.066 . .
18
21
22

Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives

Andrić, Deana; Tovilović, Gordana; Roglić, Goran; Vasković, Đurđica; Šoškić, Vukić; Tomić, Mirko; Kostić Rajačić, Slađana

(Serbian Chemical Society, 2007)

TY  - JOUR
AU  - Andrić, Deana
AU  - Tovilović, Gordana
AU  - Roglić, Goran
AU  - Vasković, Đurđica
AU  - Šoškić, Vukić
AU  - Tomić, Mirko
AU  - Kostić Rajačić, Slađana
PY  - 2007
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/313
AB  - Six newly synthesized heterocyclic (2-nitrophenyl)piperazines, with a specific structure of the heteroaryl group, whichmimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles), were evaluated for their binding affinity to rat dopamine (DA), serotonin (5-HT) and _1 receptors. All compounds with a benzimidazole group had a 5-HT2A/D2 receptors binding ratio characteristic for atypical neuroleptics (>1, pK i values). Compound 7c, 4-bromo-6-{2-_4-(2-nitrophenyl)piperazin- 1-yl_ethyl}-1H-benzimidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations.
AB  - Sintetisano je šest heterocikličnih (2-nitrofenil)piperazina sa specifičnom heteroaril grupom, koja podražava kateholsku grupu dopamina (benzimidazoli i supstituisani benzimidazoli), i ispitan je njihov afinitet ka dopaminskim, serotoninskim i _1 receptorima. Sva jedinjenja sa benzimidazolskim grupama su pokazala 5-HT 1A/D2 odnos vezivanja karakterističan za atipične neuroleptike (>1, pK i vrednosti). Jedinjenje 7c, 4-bromo-6-{2-_4-(2-nitrofenil)piperazin-1-il_etil}-1H-benzimidazol, pokazalo je izraženiji afinitet ka svim klasama receptora u poređenju sa klozapinom i takođe predstavlja jedinjenje sa najboljim karakteristikama za dalja in vivo istraživanja.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives
T1  - Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina
VL  - 72
IS  - 5
SP  - 429
EP  - 435
DO  - 10.2298/JSC0705429A
ER  - 
@article{
author = "Andrić, Deana and Tovilović, Gordana and Roglić, Goran and Vasković, Đurđica and Šoškić, Vukić and Tomić, Mirko and Kostić Rajačić, Slađana",
year = "2007",
abstract = "Six newly synthesized heterocyclic (2-nitrophenyl)piperazines, with a specific structure of the heteroaryl group, whichmimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles), were evaluated for their binding affinity to rat dopamine (DA), serotonin (5-HT) and _1 receptors. All compounds with a benzimidazole group had a 5-HT2A/D2 receptors binding ratio characteristic for atypical neuroleptics (>1, pK i values). Compound 7c, 4-bromo-6-{2-_4-(2-nitrophenyl)piperazin- 1-yl_ethyl}-1H-benzimidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations., Sintetisano je šest heterocikličnih (2-nitrofenil)piperazina sa specifičnom heteroaril grupom, koja podražava kateholsku grupu dopamina (benzimidazoli i supstituisani benzimidazoli), i ispitan je njihov afinitet ka dopaminskim, serotoninskim i _1 receptorima. Sva jedinjenja sa benzimidazolskim grupama su pokazala 5-HT 1A/D2 odnos vezivanja karakterističan za atipične neuroleptike (>1, pK i vrednosti). Jedinjenje 7c, 4-bromo-6-{2-_4-(2-nitrofenil)piperazin-1-il_etil}-1H-benzimidazol, pokazalo je izraženiji afinitet ka svim klasama receptora u poređenju sa klozapinom i takođe predstavlja jedinjenje sa najboljim karakteristikama za dalja in vivo istraživanja.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives, Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina",
volume = "72",
number = "5",
pages = "429-435",
doi = "10.2298/JSC0705429A"
}
Andrić, D., Tovilović, G., Roglić, G., Vasković, Đ., Šoškić, V., Tomić, M.,& Kostić Rajačić, S.. (2007). Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 72(5), 429-435.
https://doi.org/10.2298/JSC0705429A
Andrić D, Tovilović G, Roglić G, Vasković Đ, Šoškić V, Tomić M, Kostić Rajačić S. Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives. in Journal of the Serbian Chemical Society. 2007;72(5):429-435.
doi:10.2298/JSC0705429A .
Andrić, Deana, Tovilović, Gordana, Roglić, Goran, Vasković, Đurđica, Šoškić, Vukić, Tomić, Mirko, Kostić Rajačić, Slađana, "Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives" in Journal of the Serbian Chemical Society, 72, no. 5 (2007):429-435,
https://doi.org/10.2298/JSC0705429A . .
3
3
4

6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation

Andrić, Deana; Tovilović, Gordana; Roglić, Goran; Šoškić, Vukić; Tomić, Mirko; Kostić Rajačić, Slađana

(Serbian Chemical Society, 2007)

TY  - JOUR
AU  - Andrić, Deana
AU  - Tovilović, Gordana
AU  - Roglić, Goran
AU  - Šoškić, Vukić
AU  - Tomić, Mirko
AU  - Kostić Rajačić, Slađana
PY  - 2007
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/323
AB  - Eight new compounds with halogen atom introduced into the benzimidazole- 2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihydro- 2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure-affinity requirements, have been synthesized. All the new compounds were evaluated for the in vitro binding affinity at the dopamine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioassays, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the binding of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Divergently, these compounds were without significant affinities for the D1 DA receptors. .
AB  - Sintetisano je osam novih jedinjenja kod kojih je atom halogena uveden u benzimidazol-2-tionsku dopaminergičku farmakoforu 5-[2-(4-arilpiperazin-1-il)etil]-1,3-dihidro-2N-benzimidazol-2-tiona sa arilpiperazinskim delom molekula izabranim shodno pozna- tim zahtevima o odnosu strukture i reaktivnosti. Za sva novosintetisana jedinjenja je određen afinitet vezivanja za dopaminske (D1 i D2) i 5-NT1A receptore u in vitro eksperimentima kompeticije sa radioligandima. Kao izvor dopaminskih i 5-NT1A receptora su korištene sinaptozomalne membrane izolovane iz goveđeg nukleusa kaudatusa i hipokampusa. Sva novosintetisana jedinjenja pokazala su se kao jaki kompetitori [3H]spiperona i [3H]8-OH-DPAT, od kojih najaktivnija (9.1b i 9.2b) poseduju 34 i 170 puta veći afinitet ka D2 DA receptorima od polaznih, nehalogenovanih jedinjenja. Sa druge strane, ova jedinjenja ne poseduju značajan afinitet ka D1 dopaminskim receptorima. .
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation
T1  - 6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje
VL  - 72
IS  - 8-9
SP  - 747
EP  - 755
DO  - 10.2298/JSC0709747A
ER  - 
@article{
author = "Andrić, Deana and Tovilović, Gordana and Roglić, Goran and Šoškić, Vukić and Tomić, Mirko and Kostić Rajačić, Slađana",
year = "2007",
abstract = "Eight new compounds with halogen atom introduced into the benzimidazole- 2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihydro- 2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure-affinity requirements, have been synthesized. All the new compounds were evaluated for the in vitro binding affinity at the dopamine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioassays, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the binding of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Divergently, these compounds were without significant affinities for the D1 DA receptors. ., Sintetisano je osam novih jedinjenja kod kojih je atom halogena uveden u benzimidazol-2-tionsku dopaminergičku farmakoforu 5-[2-(4-arilpiperazin-1-il)etil]-1,3-dihidro-2N-benzimidazol-2-tiona sa arilpiperazinskim delom molekula izabranim shodno pozna- tim zahtevima o odnosu strukture i reaktivnosti. Za sva novosintetisana jedinjenja je određen afinitet vezivanja za dopaminske (D1 i D2) i 5-NT1A receptore u in vitro eksperimentima kompeticije sa radioligandima. Kao izvor dopaminskih i 5-NT1A receptora su korištene sinaptozomalne membrane izolovane iz goveđeg nukleusa kaudatusa i hipokampusa. Sva novosintetisana jedinjenja pokazala su se kao jaki kompetitori [3H]spiperona i [3H]8-OH-DPAT, od kojih najaktivnija (9.1b i 9.2b) poseduju 34 i 170 puta veći afinitet ka D2 DA receptorima od polaznih, nehalogenovanih jedinjenja. Sa druge strane, ova jedinjenja ne poseduju značajan afinitet ka D1 dopaminskim receptorima. .",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation, 6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje",
volume = "72",
number = "8-9",
pages = "747-755",
doi = "10.2298/JSC0709747A"
}
Andrić, D., Tovilović, G., Roglić, G., Šoškić, V., Tomić, M.,& Kostić Rajačić, S.. (2007). 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 72(8-9), 747-755.
https://doi.org/10.2298/JSC0709747A
Andrić D, Tovilović G, Roglić G, Šoškić V, Tomić M, Kostić Rajačić S. 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society. 2007;72(8-9):747-755.
doi:10.2298/JSC0709747A .
Andrić, Deana, Tovilović, Gordana, Roglić, Goran, Šoškić, Vukić, Tomić, Mirko, Kostić Rajačić, Slađana, "6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation" in Journal of the Serbian Chemical Society, 72, no. 8-9 (2007):747-755,
https://doi.org/10.2298/JSC0709747A . .
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