Design, synthesis and evaluation of novel thienopyrimidine-based agents bearing diaryl urea functionality as potential inhibitors of angiogenesis

Abstract

Inhibition of angiogenesis is a promising strategy for the treatment of cancer. Herein, we describe the design and synthesis of thieno[2,3-d]pyrimidine-1,3,4-thiadiazole-aryl urea derivatives 11a-m to evaluate their efficacy in the chick chorioallantoic membrane (CAM) assay. Among target agents, 11i had a considerable activity against prostate cancer cell line, PC3 (IC₅₀ = 3.6 μM). Moreover, induction of apoptosis, good inhibitory activity against the growth of capillary blood vessels, and inhibition of VEGFR-2 phosphorylation were noticeable parameters which convinced us that 11i could be considered as a promising candidate for the discovery of novel drugs to treat tumors, particularly prostate cancer.

Keywords: 1,3,4-Thiadiazole; Angiogenesis; Apoptosis; CAM assay; PC3; Thieno[2,3-d]pyrimidine; VEGFR-2.