Synthesis, biological evaluation and molecular docking studies of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan as potential antitumor agents

A series of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan (2a–2s) have been synthesized to screen for FAK inhibitory activity. Compound 2p showed the most potent biological activity against HEPG2 cancer cell line (EC50 = 10.28 μg/mL for HEPG2 and EC50 = 10.79 μM for FAK), which was comparable to the positive control. Docking simulation was performed to position compound 2p into the FAK structure active site to determine the probable binding model. The results of antiproliferative and Western-blot assay demonstrated that compound 2p possessed good antiproliferative activity against HEPG2 cancer cell line. Therefore, compound 2p with potent FAK inhibitory activity may be a potential anticancer agent against HEPG2 cancer cell.

Graphical abstractCompound 2p displayed the most potent FAK inhibitory activity with EC50 of 10.79 μM, which was comparable to the positive control staurosporine. Molecular docking study indicated that compound 2p was nicely bound to the FAK with two hydrogen bonds, and Gly/Ile were very important residues in FAK.Compound 2p also showed significant antiproliferative activity against HEPG2 with EC50 of 10.28 μM. The results of apoptosis and Western-blot assay demonstrated that compound 2p would be a potential anticancer agent against HEPG2 cancer cell.Figure optionsDownload full-size imageDownload as PowerPoint slide