Synthesis, biological evaluation and docking studies of benzoxazoles derived from thymoquinone

Glamočlija, Una (author), Padhye, Subhash (author), Špirtović-Halilović, Selma (author), Osmanović, Amar (author), Veljović, Elma (author), Roca, Sunčica (author), Novaković, Irena (author), Mandić, Boris (author), Turel, Iztok (author), Kljun, Jakob (author), Trifunović, Snežana (author), Kahrović, Emira (author), Kraljević-Pavelić, Sandra (author), Harej, Anja (author), Klobučar, Marko (author), Završnik, Davorka (author)

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 ($^1$H, $^{13}$C) 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 β) 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.

• Language: English
• Keywords: thymoquinone, benzoxazoles, anticancer activity, antimicrobial activity, western blotting, molecular docking
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2018
• Number of pages: 17 str.
• Numbering: Vol. 23, iss. 12, art. 3297
• PID: 20.500.12556/RUL-131999
• UDC: 547.78.057
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules23123297
• COBISS.SI-ID: 1538073795
• Publication date in RUL: 08.10.2021

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 12.12.2018

Secondary language

• Language: Slovenian
• Keywords: benzoksazoli, timokinon, protimikrobno delovanje, protirakavo delovanje

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Ministarstvo za obrazovanje, nauku, kulturu i sport FBiH
• Project number: 05-39-3629-1/14
• Name: Modeliranje i doking studije novih potentnih azometinskih derivata timokinona i njihovih organometalnih kompleksa

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0175
• Name: Napredna anorganska kemija