Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone

2018
Authors
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
Article (Published version)
Metadata
Show full item recordAbstract
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 h...ave 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.
Keywords:
thymoquinone / benzoxazoles / anticancer activity / antimicrobial activity / western blotting / molecular dockingSource:
Molecules, 2018, 23, 12Publisher:
- MDPI
Funding / projects:
- Federal Ministry of education and science in Bosnia and Herzegovina - 05-39-3629-1/14
- Ministarstvo za obrazovanje, nauku, kulturu i sport FBiH, 2014-2015 - 05-39-3629-1/14
DOI: 10.3390/molecules23123297
ISSN: 1420-3049
PubMed: 30545123
WoS: 000454523000247
Scopus: 2-s2.0-85058766907
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Institution/Community
IHTMTY - 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 . .