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

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

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.

• Jezik: Angleški jezik
• Ključne besede: thymoquinone, benzoxazoles, anticancer activity, antimicrobial activity, western blotting, molecular docking
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2018
• Št. strani: 17 str.
• Številčenje: Vol. 23, iss. 12, art. 3297
• PID: 20.500.12556/RUL-131999
• UDK: 547.78.057
• ISSN pri članku: 1420-3049
• DOI: 10.3390/molecules23123297
• COBISS.SI-ID: 1538073795
• Datum objave v RUL: 08.10.2021

Gradivo je del revije

• Naslov: Molecules
• Skrajšan naslov: Molecules
• Založnik: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 12.12.2018

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: benzoksazoli, timokinon, protimikrobno delovanje, protirakavo delovanje

Projekti

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Ministarstvo za obrazovanje, nauku, kulturu i sport FBiH
• Številka projekta: 05-39-3629-1/14
• Naslov: Modeliranje i doking studije novih potentnih azometinskih derivata timokinona i njihovih organometalnih kompleksa

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0175
• Naslov: Napredna anorganska kemija