A new class of human fatty acid synthase inhibitors: Synthesis and their anticancer evaluation

摘要

A series of 3-pentadecyl/heptadecyl-6-subsituted phenyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles have been designed, synthesized and screened for their in?vitro antitumour activity against breast cancer cell lines. Three compounds namely, 3-pentadecyl-6-phenyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (6e), 3-heptadecyl-6-phenyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (6j) and 3-heptadecyl-6(3-nitrophenyl)[1,2,4]triazolo[3,4b][1,3,4]-thiadiazole (6g) have displayed comparable activities towards human breast cancer lines. Molecular docking studies have been carried out on the crystal structure of human fatty acid synthase thioesterase domain (2PX6) by using GLIDE integrated Maestro?9.3 version. The designed compounds have shown good binding interactions with the active site residues present in the enzyme and have given very good G-scores when compared to the known inhibitor orlistat.