Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers. (31st December 2022)

• Record Type: Journal Article
• Authors: Eissa, Ibrahim H.; El-Haggar, Radwan; Dahab, Mohammed A.; Ahmed, Marwa F.; Mahdy, Hazem A.; Alsantali, Reem I.; Elwan, Alaa; Masurier, Nicolas; Fatahala, Samar S.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 37:Number 1(2022)
• Page Start: 1587
• Page End: 1599
• Publication Date: 2022-12-31
• Subjects: Benzoxazole-benzamide -- anti-cancer -- apoptosis -- VEGFR-2 inhibitors -- Bcl-2; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2081844
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates 1 –15 was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxicity was estimated using normal human fibroblast (WI-38) cells. Compounds 1, 9 –12 and 15 showed good selectivity and displayed excellent cytotoxic activity against both HCT-116 and MCF-7 cancer cell lines compared to sorafenib, used as a reference compound. Furthermore, compounds 1 and 11 showed potent VEGFR-2 inhibitory activity. The cell cycle progression assay showed that 1 and 11 induced cell cycle arrest at G2/M phase, with a concomitant increase in the pre-G1 cell population. Further pharmacological studies showed that 1 and 11 induced apoptosis and inhibited the expression of the anti-apoptotic Bcl-2 and Bcl-xL proteins in both cell lines. Therefore, compounds 1 and 11 might serve as promising candidates for future anticancer therapy development.