TY  - JOUR
AU  - Glamoclija, Una
AU  - Padhye, Subhash
AU  - Spirtovic-Halilovic, Selma
AU  - Osmanovic, Amar
AU  - Veljović, Elma
AU  - Roca, Suncica
AU  - Novaković, Irena
AU  - Mandić, Boris
AU  - Turel, Iztok
AU  - Kljun, Jakob
AU  - Trifunović, Snežana
AU  - Kahrovic, Emira
AU  - Kraljević Pavelić, Sandra
AU  - Harej, Anja
AU  - Klobucar, Marko
AU  - Zavrsnik, Davorka
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2403
AB  - Thymoquinone (TQ), a natural compound with antimicrobial and antitumor activity, was used as the starting molecule for the preparation of 3-aminothymoquinone (ATQ) from which ten novel benzoxazole derivatives were prepared and characterized by elemental analysis, IR spectroscopy, mass spectrometry and NMR (H-1, C-13) spectroscopy in solution. The crystal structure of 4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazole-5-ol (1a) has been determined by X-ray diffraction. All compounds were tested for their antibacterial, antifungal and antitumor activities. TQ and ATQ showed better antibacterial activity against tested Gram-positive and Gram-negative bacterial strains than benzoxazoles. ATQ had the most potent antifungal effect against Candida albicans, Saccharomyces cerevisiae and Aspergillus brasiliensis. Three benzoxazole derivatives and ATQ showed the highest antitumor activities. The most potent was 2-(4-fluorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1f). Western blot analyses have shown that this compound inhibited phosphorylation of protein kinase B (Akt) and Insulin-like Growth Factor-1 Receptor (IGF1R ) in HeLa and HepG2 cells. The least toxic compound against normal fibroblast cells, which maintains similar antitumor activities as TQ, was 2-(4-chlorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1e). Docking studies indicated that 1e and 1f have significant effects against selected receptors playing important roles in tumour survival.
PB  - MDPI
T2  - Molecules
T1  - Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone
VL  - 23
IS  - 12
DO  - 10.3390/molecules23123297
ER  - 

@article{
author = "Glamoclija, Una and Padhye, Subhash and Spirtovic-Halilovic, Selma and Osmanovic, Amar and Veljović, Elma and Roca, Suncica and Novaković, Irena and Mandić, Boris and Turel, Iztok and Kljun, Jakob and Trifunović, Snežana and Kahrovic, Emira and Kraljević Pavelić, Sandra and Harej, Anja and Klobucar, Marko and Zavrsnik, Davorka",
year = "2018",
abstract = "Thymoquinone (TQ), a natural compound with antimicrobial and antitumor activity, was used as the starting molecule for the preparation of 3-aminothymoquinone (ATQ) from which ten novel benzoxazole derivatives were prepared and characterized by elemental analysis, IR spectroscopy, mass spectrometry and NMR (H-1, C-13) spectroscopy in solution. The crystal structure of 4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazole-5-ol (1a) has been determined by X-ray diffraction. All compounds were tested for their antibacterial, antifungal and antitumor activities. TQ and ATQ showed better antibacterial activity against tested Gram-positive and Gram-negative bacterial strains than benzoxazoles. ATQ had the most potent antifungal effect against Candida albicans, Saccharomyces cerevisiae and Aspergillus brasiliensis. Three benzoxazole derivatives and ATQ showed the highest antitumor activities. The most potent was 2-(4-fluorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1f). Western blot analyses have shown that this compound inhibited phosphorylation of protein kinase B (Akt) and Insulin-like Growth Factor-1 Receptor (IGF1R ) in HeLa and HepG2 cells. The least toxic compound against normal fibroblast cells, which maintains similar antitumor activities as TQ, was 2-(4-chlorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1e). Docking studies indicated that 1e and 1f have significant effects against selected receptors playing important roles in tumour survival.",
publisher = "MDPI",
journal = "Molecules",
title = "Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone",
volume = "23",
number = "12",
doi = "10.3390/molecules23123297"
}

Glamoclija, U., Padhye, S., Spirtovic-Halilovic, S., Osmanovic, A., Veljović, E., Roca, S., Novaković, I., Mandić, B., Turel, I., Kljun, J., Trifunović, S., Kahrovic, E., Kraljević Pavelić, S., Harej, A., Klobucar, M.,& Zavrsnik, D.. (2018). Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone. in Molecules
MDPI., 23(12).
https://doi.org/10.3390/molecules23123297

Glamoclija U, Padhye S, Spirtovic-Halilovic S, Osmanovic A, Veljović E, Roca S, Novaković I, Mandić B, Turel I, Kljun J, Trifunović S, Kahrovic E, Kraljević Pavelić S, Harej A, Klobucar M, Zavrsnik D. Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone. in Molecules. 2018;23(12).
doi:10.3390/molecules23123297 .

Glamoclija, Una, Padhye, Subhash, Spirtovic-Halilovic, Selma, Osmanovic, Amar, Veljović, Elma, Roca, Suncica, Novaković, Irena, Mandić, Boris, Turel, Iztok, Kljun, Jakob, Trifunović, Snežana, Kahrovic, Emira, Kraljević Pavelić, Sandra, Harej, Anja, Klobucar, Marko, Zavrsnik, Davorka, "Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone" in Molecules, 23, no. 12 (2018),
https://doi.org/10.3390/molecules23123297 . .

TY  - JOUR
AU  - Malatesti, Nela
AU  - Harej, Anja
AU  - Kraljević Pavelić, Sandra
AU  - Lončarić, M.
AU  - Zorc, H.
AU  - Wittine, Karlo
AU  - Anđelković, Uroš
AU  - Josić, Djuro
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6916
AB  - Photodynamic therapy (PDT) is a treatment that aims to kill cancer cells by reactive oxygen species, mainly singlet oxygen, produced through light activation of a photosensitiser (PS). Amongst photosensitisers that attracted the most attention in the last decade are cationic and amphiphilic molecules based on porphyrin, chlorin and phthalocyanine structures. Our aim was to join this search for more optimal balance of the lipophilic and hydrophilic moieties in a PS. A new amphiphilic porphyrin, 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (5) was synthesised and characterised by 1H NMR, UV–vis and fluorescence spectroscopy, and by MALDI-TOF/TOF spectrometry. In vitro photodynamic activity of 5 was evaluated on HeLa cell lines and compared to the activity of the hydrophilic 5-(4-acetamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (7). Low fluence rate (2 mW cm−2) of red light (643 nm) was used for the activation, and both porphyrins showed a drug dose-response as well as a light dose-response relationship, but the amphiphilic porphyrin was presented with significantly lower IC50 values. The obtained IC50 values for 5 were 1.4 μM at 15 min irradiation time and 0.7 μM when the time of irradiation was 30 min, while for 7 these values were 37 and 6 times higher, respectively. These results confirm the importance of the lipophilic component in a PS and show a potential for 5 to be used as a PS in PDT applications.
PB  - Elsevier
T2  - Photodiagnosis and Photodynamic Therapy
T1  - Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate
VL  - 15
SP  - 115
EP  - 126
DO  - 10.1016/j.pdpdt.2016.07.003
ER  - 

@article{
author = "Malatesti, Nela and Harej, Anja and Kraljević Pavelić, Sandra and Lončarić, M. and Zorc, H. and Wittine, Karlo and Anđelković, Uroš and Josić, Djuro",
year = "2016",
abstract = "Photodynamic therapy (PDT) is a treatment that aims to kill cancer cells by reactive oxygen species, mainly singlet oxygen, produced through light activation of a photosensitiser (PS). Amongst photosensitisers that attracted the most attention in the last decade are cationic and amphiphilic molecules based on porphyrin, chlorin and phthalocyanine structures. Our aim was to join this search for more optimal balance of the lipophilic and hydrophilic moieties in a PS. A new amphiphilic porphyrin, 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (5) was synthesised and characterised by 1H NMR, UV–vis and fluorescence spectroscopy, and by MALDI-TOF/TOF spectrometry. In vitro photodynamic activity of 5 was evaluated on HeLa cell lines and compared to the activity of the hydrophilic 5-(4-acetamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (7). Low fluence rate (2 mW cm−2) of red light (643 nm) was used for the activation, and both porphyrins showed a drug dose-response as well as a light dose-response relationship, but the amphiphilic porphyrin was presented with significantly lower IC50 values. The obtained IC50 values for 5 were 1.4 μM at 15 min irradiation time and 0.7 μM when the time of irradiation was 30 min, while for 7 these values were 37 and 6 times higher, respectively. These results confirm the importance of the lipophilic component in a PS and show a potential for 5 to be used as a PS in PDT applications.",
publisher = "Elsevier",
journal = "Photodiagnosis and Photodynamic Therapy",
title = "Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate",
volume = "15",
pages = "115-126",
doi = "10.1016/j.pdpdt.2016.07.003"
}

Malatesti, N., Harej, A., Kraljević Pavelić, S., Lončarić, M., Zorc, H., Wittine, K., Anđelković, U.,& Josić, D.. (2016). Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate. in Photodiagnosis and Photodynamic Therapy
Elsevier., 15, 115-126.
https://doi.org/10.1016/j.pdpdt.2016.07.003

Malatesti N, Harej A, Kraljević Pavelić S, Lončarić M, Zorc H, Wittine K, Anđelković U, Josić D. Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate. in Photodiagnosis and Photodynamic Therapy. 2016;15:115-126.
doi:10.1016/j.pdpdt.2016.07.003 .

Malatesti, Nela, Harej, Anja, Kraljević Pavelić, Sandra, Lončarić, M., Zorc, H., Wittine, Karlo, Anđelković, Uroš, Josić, Djuro, "Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate" in Photodiagnosis and Photodynamic Therapy, 15 (2016):115-126,
https://doi.org/10.1016/j.pdpdt.2016.07.003 . .