Harnessing potential COX-2 engagement for boosting anticancer activity of substituted 2-mercapto-4(3H)-quinazolinones with promising EGFR/VEGFR-2 inhibitory activities.

Autor: Hamdi A; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: Abdelrahmanhamdi2012@mans.edu.eg., Tawfik SS; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Ali AR; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Ewes WA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Haikal A; Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., El-Azab AS; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia., Bakheit AH; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia., Hefnawy MM; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia., Ghabbour HA; School of Health and Biomedical Sciences, RMIT University, Melbourne 3083, Australia., Abdel-Aziz AA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Dec; Vol. 153, pp. 107951. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1016/j.bioorg.2024.107951
Abstrakt: We designed and synthesized new quinazolinone-tethered phenyl thiourea/thiadiazole derivatives 4-26. Based on their structural characteristics, these compounds were proposed to have a multi-target mode of action for their anticancer activities. Using the MTT assay method, antiproliferative effects were assessed against three human cancer cell lines (HEPG-2, MCF-7, and HCT-116). In vitro assessment for enzymatic inhibitory activity of the most active compounds 4, 9 and 20 was done for EGFR, VEGFR-2 and COX-2 as potential targets. The screened compounds showed low micromolar IC 50 inhibitory effects against the three targets. Compound 9 demonstrated similar EGFR/VEGFR-2 inhibitory effect to the control drugs and potential inhibitory activity for COX-2 enzyme. In MCF-7 cells, the most active analog 9 caused 41.02% total apoptosis, and arrested the cell cycle at the G2/M phase. Taken as a whole, the findings of this study provide significant new understandings into the relationship between COX inhibition and cancer therapy. Furthermore, the outcomes showcased the encouraging efficacy of these compounds with a multi-target mechanism, making them excellent choices for additional research and development into possible anticancer drug.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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