Design, synthesis, in silico studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.

ABSTRACT: A novel series of pyrimidine-5-carbonitrile derivatives bearing benzylidene and hydrazone moieties with different linkers (spacers) were designed and synthesized as possible inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The newly synthesized compounds were evaluated in vitro for their cytotoxic activities against two human cancer cell lines namely colon cancer (HCT-116) and breast cancer (MCF-7) using sorafenib as a standard anticancer drug. Compounds 9d, 11e, 12b, and 12d showed higher cytotoxic activities than sorafenib with IC₅₀ values ranging from 1.14 to 10.33 μM. In particular, compound 11e exhibited excellent activities against HCT-116 and MCF-7 with IC₅₀ values of 1.14 and 1.54 μM, respectively. Moreover, compound 11e exhibi

SUBMITTER: Saleh AM 

PROVIDER: S-EPMC10363774 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature