Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Benzoxazole-Benzamide Conjugates a 2-Thioacetamido Linker As Potential Anti-proliferative Agents, VEGFR-2 Inhibitors and Apoptotic Inducers

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 May 31

PMID 35637622

Authors

Ibrahim H Eissa

Radwan El-Haggar

Mohammed A Dahab

Marwa F Ahmed

Hazem A Mahdy

Reem I Alsantali

Alaa Elwan

Nicolas Masurier

Samar S Fatahala

Affiliations

Soon will be listed here.

Abstract

A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates - 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 , - and 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 and showed potent VEGFR-2 inhibitory activity. The cell cycle progression assay showed that and induced cell cycle arrest at G2/M phase, with a concomitant increase in the pre-G1 cell population. Further pharmacological studies showed that and induced apoptosis and inhibited the expression of the anti-apoptotic Bcl-2 and Bcl-xL proteins in both cell lines. Therefore, compounds and might serve as promising candidates for future anticancer therapy development.

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