Synthesis, biological evaluation, and molecular docking studies of cinnamic acyl 1,3,4-thiadiazole amide derivatives as novel antitubulin agents

A series of cinnamic acyl 1,3,4-thiadiazole amide derivatives (6a–10e) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and tubulin polymerization inhibitors. Among all the compounds, 10e showed the most potent activity in vitro, which inhibited the growth of MCF-7 and A549 cell lines with IC50 values of 0.28 and 0.52 μg/mL, respectively. Compound 10e also exhibited significant tubulin polymerization inhibitory activity (IC50 = 1.16 μg/mL). Docking simulation was performed to insert compound 10e into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10e with potent inhibitory activity in tumor growth may be a potential anticancer agent.

A series of cinnamic acyl 1,3,4-thiadiazole amide derivatives have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and tubulin polymerization inhibitors. Compound 10e possessed the most potent tubulin polymerization inhibitory activity (IC50 = 1.16 μg/mL) and anticancer activities (IC50 = 0.28 μg/mL for MCF-7 and IC50 = 0.52 μg/mL for A549). Docking simulation was performed to insert compound 10e into the crystal structure of tubulin to determine the probable binding model.Figure optionsDownload as PowerPoint slide