Design, Synthesis, and Biological Evaluation of 1-(5-(Benzylthio)-1,3,4-Thiadiazol-2-Yl)-3-Phenylurea Derivatives As Anticancer Agents Publisher



Aghcheli A¹ ; Toolabi M² ; Ayati A³ ; Moghimi S³ ; Firoozpour L³ ; Bakhshaiesh TO⁴ ; Nazeri E⁴ ; Norouzbahari M⁵ ; Esmaeili R⁴ ; Foroumadi A^{1, 3}
Source: Medicinal Chemistry Research Published:2020

Abstract

A novel series of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives (5a–l) were designed and synthesized as sorafenib analogs. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, HepG2, A549, and HeLa cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells. In particular, 2-F, 4-Cl, and 2,6-diF substituted derivatives (5d, 5g, and 5k) showed promising activities, especially against Hela cancer cells (IC50 = 0.37, 0.73 and 0.95 µM, respectively) which were significantly more potent than sorafenib as the reference drug (IC50 = 7.91 µM). Flow cytometry analysis revealed that the prototype compounds (5d, 5g, and 5k) significantly induced apoptotic cell death in HeLa cancer cells and blocked the cell cycle at the sub-G1 phase. Moreover, in silico docking study confirmed the binding of the prototype compound to the active site of VEGFR-2. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.