Synthesis and evaluation of new thiourea derivatives as antitumor and antiangiogenic agents

A series of novel thiourea derivatives were synthesized and evaluated by biological activities. Among them, compound 10e containing 3,5-bis(trifluoromethyl)phenyl moiety (R-1) at the terminal thiourea and phenylamino (R-2) at the terminal acyl position showed the best cytotoxic activities against seven cancer cell lines (NCI-H460, Colo-205, HCT116, MDA-MB-231, MCF-7, HepG2, PLC/PRF/5) and HUVECs. Moreover, compound 10e moderately inhibited various RTKs such as VEGFR2, VEGFR3, and PDGFR beta. Notably, 10e exhibited much better inhibitory effect of tumor formation and antiangiogenic activities than Sorafenib and Regorafenib at the same concentration. Further docking studies suggested that 10e could serve as potential candidate for cancer therapy. (C) 2020 Elsevier Ltd. All rights reserved.