Obtaining, physicochemical characterization, analysis and biological activity of pharmacologically active compounds

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Obtaining, physicochemical characterization, analysis and biological activity of pharmacologically active compounds (en)
Добијање, физичко-хемијска карактеризација, аналитика и биолошка активност фармаколошки активних супстанци (sr)
Dobijanje, fizičko-hemijska karakterizacija, analitika i biološka aktivnost farmakološki aktivnih supstanci (sr_RS)
Authors

Publications

Synthesis and DNase I inhibitory properties of new benzocyclobutane-2,5-diones

Bondžić, Bojan; Džambaski, Zdravko; Kolarević, Ana; Đorđević, Aleksandra; Anderluh, Marko; Šmelcerović, Andrija

(Future Medicine Ltd., 2019)

TY  - JOUR
AU  - Bondžić, Bojan
AU  - Džambaski, Zdravko
AU  - Kolarević, Ana
AU  - Đorđević, Aleksandra
AU  - Anderluh, Marko
AU  - Šmelcerović, Andrija
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3957
AB  - Eight new benzocyclobutane-2,5-diones (1a–1h) were synthesized, and their inhibitory properties
against bovine pancreatic DNase I were examined in vitro. Methods & results: Compounds 1a–1h
were synthesized using photocycloaddition of duroquinone with various phenyl-substituted ethylenes
in the presence of 18W compact fluorescent lamp (visible light). Two compounds, 1,3,4,6-tetramethyl-7-
phenylbicyclo[4.2.0]oct-3-ene-2,5-dione (1a) and 1,3,4,6-tetramethyl-7-p-tolylbicyclo[4.2.0]oct-3-ene-2,5-
dione (1b) inhibited DNase I in a noncompetitive manner with IC50 values below 150 μM and showed to
be more potent DNase I inhibitors than crystal violet, used as a positive control. In order to analyze potential
binding sites for the studied compounds with DNase I, molecular docking study was performed.
Conclusion: The studied benzocyclobutane-2,5-diones offer a good starting point for a design of new
DNase I inhibitors.
PB  - Future Medicine Ltd.
T2  - Future Medicinal Chemistry
T1  - Synthesis and DNase I inhibitory properties of new benzocyclobutane-2,5-diones
VL  - 11
VL  - 2426
IS  - 18
SP  - 2415
DO  - 10.4155/fmc-2019-0032
ER  - 
@article{
author = "Bondžić, Bojan and Džambaski, Zdravko and Kolarević, Ana and Đorđević, Aleksandra and Anderluh, Marko and Šmelcerović, Andrija",
year = "2019",
abstract = "Eight new benzocyclobutane-2,5-diones (1a–1h) were synthesized, and their inhibitory properties
against bovine pancreatic DNase I were examined in vitro. Methods & results: Compounds 1a–1h
were synthesized using photocycloaddition of duroquinone with various phenyl-substituted ethylenes
in the presence of 18W compact fluorescent lamp (visible light). Two compounds, 1,3,4,6-tetramethyl-7-
phenylbicyclo[4.2.0]oct-3-ene-2,5-dione (1a) and 1,3,4,6-tetramethyl-7-p-tolylbicyclo[4.2.0]oct-3-ene-2,5-
dione (1b) inhibited DNase I in a noncompetitive manner with IC50 values below 150 μM and showed to
be more potent DNase I inhibitors than crystal violet, used as a positive control. In order to analyze potential
binding sites for the studied compounds with DNase I, molecular docking study was performed.
Conclusion: The studied benzocyclobutane-2,5-diones offer a good starting point for a design of new
DNase I inhibitors.",
publisher = "Future Medicine Ltd.",
journal = "Future Medicinal Chemistry",
title = "Synthesis and DNase I inhibitory properties of new benzocyclobutane-2,5-diones",
volume = "11, 2426",
number = "18",
pages = "2415",
doi = "10.4155/fmc-2019-0032"
}
Bondžić, B., Džambaski, Z., Kolarević, A., Đorđević, A., Anderluh, M.,& Šmelcerović, A.. (2019). Synthesis and DNase I inhibitory properties of new benzocyclobutane-2,5-diones. in Future Medicinal Chemistry
Future Medicine Ltd.., 11(18), 2415.
https://doi.org/10.4155/fmc-2019-0032
Bondžić B, Džambaski Z, Kolarević A, Đorđević A, Anderluh M, Šmelcerović A. Synthesis and DNase I inhibitory properties of new benzocyclobutane-2,5-diones. in Future Medicinal Chemistry. 2019;11(18):2415.
doi:10.4155/fmc-2019-0032 .
Bondžić, Bojan, Džambaski, Zdravko, Kolarević, Ana, Đorđević, Aleksandra, Anderluh, Marko, Šmelcerović, Andrija, "Synthesis and DNase I inhibitory properties of new benzocyclobutane-2,5-diones" in Future Medicinal Chemistry, 11, no. 18 (2019):2415,
https://doi.org/10.4155/fmc-2019-0032 . .
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Synthesis and DNase I inhibitory properties of some 4‐thiazolidinone derivatives

Kolarević, Ana; Ilić, Budimir S.; Kocić, Gordana; Džambaski, Zdravko; Šmelcerović, Andrija; Bondžić, Bojan

(Wiley, 2018)

TY  - JOUR
AU  - Kolarević, Ana
AU  - Ilić, Budimir S.
AU  - Kocić, Gordana
AU  - Džambaski, Zdravko
AU  - Šmelcerović, Andrija
AU  - Bondžić, Bojan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2998
AB  - Twelve new thiazolidinones were synthesized and, together with 41 previously
synthesized thiazolidinones, evaluated for inhibitory activity against deoxyribonuclease I (DNase I) in vitro. Ten compounds inhibited commercial bovine pancreatic DNase I with an IC50 below 200 μM and showed to be more potent DNase I inhibitors than crystal violet (IC50 = 365.90 ± 47.33 μM), used as a positive control. Moreover, three compounds were active against DNase I in rat
liver homogenate, having an IC50 below 200 μM. (3‐Methyl‐1,4‐dioxothiazolidin‐2‐ylidene)‐N‐(2‐phenylethyl)ethanamide (41) exhibited the most potent DNase I inhibition against both commercial and rat liver DNase I with IC50 values of 115.96 ± 11.70 and 151.36 ± 15.85 μM, respectively. Site Finder and molecular docking defined the thiazolidinones interactions with the most important catalytic residues of DNase I, including the H‐acceptor interaction with residues His 134 and His 252 and/or H‐donor interaction with residues Glu 39 and Asp 168. The three most active compounds against both commercial and rat liver DNase I (31, 38, and 41) exhibited favorable physico‐chemical, pharmacokinetic, and toxicological properties. These observations could be
utilized to guide the rational design and optimization of novel thiazolidinone inhibitors. Thiazolidinones as novel DNase I inhibitors could have potential therapeutic applications due to the significant involvement of DNase I in the pathophysiology of many disease conditions.
PB  - Wiley
T2  - Journal of Cellular Biochemistry
T1  - Synthesis and DNase I inhibitory properties of some 4‐thiazolidinone derivatives
VL  - 120
IS  - 1
SP  - 264
EP  - 274
DO  - 10.1002/jcb.27339
ER  - 
@article{
author = "Kolarević, Ana and Ilić, Budimir S. and Kocić, Gordana and Džambaski, Zdravko and Šmelcerović, Andrija and Bondžić, Bojan",
year = "2018",
abstract = "Twelve new thiazolidinones were synthesized and, together with 41 previously
synthesized thiazolidinones, evaluated for inhibitory activity against deoxyribonuclease I (DNase I) in vitro. Ten compounds inhibited commercial bovine pancreatic DNase I with an IC50 below 200 μM and showed to be more potent DNase I inhibitors than crystal violet (IC50 = 365.90 ± 47.33 μM), used as a positive control. Moreover, three compounds were active against DNase I in rat
liver homogenate, having an IC50 below 200 μM. (3‐Methyl‐1,4‐dioxothiazolidin‐2‐ylidene)‐N‐(2‐phenylethyl)ethanamide (41) exhibited the most potent DNase I inhibition against both commercial and rat liver DNase I with IC50 values of 115.96 ± 11.70 and 151.36 ± 15.85 μM, respectively. Site Finder and molecular docking defined the thiazolidinones interactions with the most important catalytic residues of DNase I, including the H‐acceptor interaction with residues His 134 and His 252 and/or H‐donor interaction with residues Glu 39 and Asp 168. The three most active compounds against both commercial and rat liver DNase I (31, 38, and 41) exhibited favorable physico‐chemical, pharmacokinetic, and toxicological properties. These observations could be
utilized to guide the rational design and optimization of novel thiazolidinone inhibitors. Thiazolidinones as novel DNase I inhibitors could have potential therapeutic applications due to the significant involvement of DNase I in the pathophysiology of many disease conditions.",
publisher = "Wiley",
journal = "Journal of Cellular Biochemistry",
title = "Synthesis and DNase I inhibitory properties of some 4‐thiazolidinone derivatives",
volume = "120",
number = "1",
pages = "264-274",
doi = "10.1002/jcb.27339"
}
Kolarević, A., Ilić, B. S., Kocić, G., Džambaski, Z., Šmelcerović, A.,& Bondžić, B.. (2018). Synthesis and DNase I inhibitory properties of some 4‐thiazolidinone derivatives. in Journal of Cellular Biochemistry
Wiley., 120(1), 264-274.
https://doi.org/10.1002/jcb.27339
Kolarević A, Ilić BS, Kocić G, Džambaski Z, Šmelcerović A, Bondžić B. Synthesis and DNase I inhibitory properties of some 4‐thiazolidinone derivatives. in Journal of Cellular Biochemistry. 2018;120(1):264-274.
doi:10.1002/jcb.27339 .
Kolarević, Ana, Ilić, Budimir S., Kocić, Gordana, Džambaski, Zdravko, Šmelcerović, Andrija, Bondžić, Bojan, "Synthesis and DNase I inhibitory properties of some 4‐thiazolidinone derivatives" in Journal of Cellular Biochemistry, 120, no. 1 (2018):264-274,
https://doi.org/10.1002/jcb.27339 . .
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Effect of four lichen acids isolated from Hypogymnia physodes on viability of rat thymocytes

Pavlovic, Voja; Stojanovic, Igor; Jadranin, Milka; Vajs, Vlatka; Đorđević, Iris; Smelcerovic, Andrija; Stojanovic, Gordana

(Oxford : Pergamon-Elsevier Science Ltd, 2013)

TY  - JOUR
AU  - Pavlovic, Voja
AU  - Stojanovic, Igor
AU  - Jadranin, Milka
AU  - Vajs, Vlatka
AU  - Đorđević, Iris
AU  - Smelcerovic, Andrija
AU  - Stojanovic, Gordana
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1281
AB  - Four lichen acids, physodalic acid (F1), physodic acid (F2), 3-hydroxyphysodic acid (F3), and isophysodic acid (F4), were isolated from Hypogymnia physodes methanol extract using preparative reversed-phase high performance liquid chromatography and their structures were determined by UV, MS, H-1 NMR and C-13 NMR. This is the first report on the isolation of F4 from H. physodes. Isolated rat thymocytes were cultivated with increasing F1-F4 concentrations (0.1, 1, 10 mu g/well) and proliferative activity, viability, ROS (reactive oxygen species) production and MMP (mitochondrial membrane potential) disturbances were evaluated. Obtained results show significantly decreased thymocytes proliferation was observed when cells were treated with F1 (1 mu g, p  LT  0.05; 10 mu g; p  LT  0.001), F2 (10 mu g, p  LT  0.05) and F3 compound (10 mu g, p  LT  0.05). Significantly increased cytotoxicity was detected when cells were incubated with F1 (1 mu g, p  LT  0.05; 10 mu g, p  LT  0.01), F2 (10 mu g, p  LT  0.05) and F3 compound (10 mu g, p  LT  0.001). Increased H2DCF-DA fluorescence intensity, when cells were treated with F1 (1 mu g, p  LT  0.001; 1 mu g, p  LT  0.01; 10 mu g, p  LT  0.001) and F2 (1 mu g, p  LT  0.05; 10 mu g, p  LT  0.01) compound, indicating the increase of intracellular ROS production. Simultaneously, increased ROS levels were followed with significantly decreased MMP when thymocytes were cultivated with F1 (0.1 mu g, p  LT  0.001; 1 mu g, p  LT  0.001; 10 mu g, p  LT  0.001) and F2 compound (10 mu g, p  LT  0.001). Thymocytes exposure to increased (0.1, 1, 10 mu g) concentrations of F3 and F4 compounds did not result with significant alterations in MMP and intracellular ROS production. We have shown that higher F1 and F2 concentrations induce thymocytes toxicity mainly through induction of oxidative stress, while cytotoxicity effect of F3 is followed with altered antioxidant/oxidant balance. The rigid 11H-dibenzo[b,e][1,4]dioxepin-11-one ring in the depsidone structure may play a important role for the examined biological activities.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Food and Chemical Toxicology
T1  - Effect of four lichen acids isolated from Hypogymnia physodes on viability of rat thymocytes
VL  - 51
SP  - 160
EP  - 164
DO  - 10.1016/j.fct.2012.04.043
ER  - 
@article{
author = "Pavlovic, Voja and Stojanovic, Igor and Jadranin, Milka and Vajs, Vlatka and Đorđević, Iris and Smelcerovic, Andrija and Stojanovic, Gordana",
year = "2013",
abstract = "Four lichen acids, physodalic acid (F1), physodic acid (F2), 3-hydroxyphysodic acid (F3), and isophysodic acid (F4), were isolated from Hypogymnia physodes methanol extract using preparative reversed-phase high performance liquid chromatography and their structures were determined by UV, MS, H-1 NMR and C-13 NMR. This is the first report on the isolation of F4 from H. physodes. Isolated rat thymocytes were cultivated with increasing F1-F4 concentrations (0.1, 1, 10 mu g/well) and proliferative activity, viability, ROS (reactive oxygen species) production and MMP (mitochondrial membrane potential) disturbances were evaluated. Obtained results show significantly decreased thymocytes proliferation was observed when cells were treated with F1 (1 mu g, p  LT  0.05; 10 mu g; p  LT  0.001), F2 (10 mu g, p  LT  0.05) and F3 compound (10 mu g, p  LT  0.05). Significantly increased cytotoxicity was detected when cells were incubated with F1 (1 mu g, p  LT  0.05; 10 mu g, p  LT  0.01), F2 (10 mu g, p  LT  0.05) and F3 compound (10 mu g, p  LT  0.001). Increased H2DCF-DA fluorescence intensity, when cells were treated with F1 (1 mu g, p  LT  0.001; 1 mu g, p  LT  0.01; 10 mu g, p  LT  0.001) and F2 (1 mu g, p  LT  0.05; 10 mu g, p  LT  0.01) compound, indicating the increase of intracellular ROS production. Simultaneously, increased ROS levels were followed with significantly decreased MMP when thymocytes were cultivated with F1 (0.1 mu g, p  LT  0.001; 1 mu g, p  LT  0.001; 10 mu g, p  LT  0.001) and F2 compound (10 mu g, p  LT  0.001). Thymocytes exposure to increased (0.1, 1, 10 mu g) concentrations of F3 and F4 compounds did not result with significant alterations in MMP and intracellular ROS production. We have shown that higher F1 and F2 concentrations induce thymocytes toxicity mainly through induction of oxidative stress, while cytotoxicity effect of F3 is followed with altered antioxidant/oxidant balance. The rigid 11H-dibenzo[b,e][1,4]dioxepin-11-one ring in the depsidone structure may play a important role for the examined biological activities.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Food and Chemical Toxicology",
title = "Effect of four lichen acids isolated from Hypogymnia physodes on viability of rat thymocytes",
volume = "51",
pages = "160-164",
doi = "10.1016/j.fct.2012.04.043"
}
Pavlovic, V., Stojanovic, I., Jadranin, M., Vajs, V., Đorđević, I., Smelcerovic, A.,& Stojanovic, G.. (2013). Effect of four lichen acids isolated from Hypogymnia physodes on viability of rat thymocytes. in Food and Chemical Toxicology
Oxford : Pergamon-Elsevier Science Ltd., 51, 160-164.
https://doi.org/10.1016/j.fct.2012.04.043
Pavlovic V, Stojanovic I, Jadranin M, Vajs V, Đorđević I, Smelcerovic A, Stojanovic G. Effect of four lichen acids isolated from Hypogymnia physodes on viability of rat thymocytes. in Food and Chemical Toxicology. 2013;51:160-164.
doi:10.1016/j.fct.2012.04.043 .
Pavlovic, Voja, Stojanovic, Igor, Jadranin, Milka, Vajs, Vlatka, Đorđević, Iris, Smelcerovic, Andrija, Stojanovic, Gordana, "Effect of four lichen acids isolated from Hypogymnia physodes on viability of rat thymocytes" in Food and Chemical Toxicology, 51 (2013):160-164,
https://doi.org/10.1016/j.fct.2012.04.043 . .
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