Synthesis and Biological Evaluation of Novel 1,3,4-thiadiazole Derivatives Incorporating Benzisoselenazolone Scaffold as Potential Antitumor Agents.

Abstract

Based on the biological significance of benzisoselenazolone and 1,3,4-thiadiazole, a series of novel 1,3,4-thiadiazole derivatives incorporating benzisoselenazolone scaffold were designed and synthesized with ebselen as a lead compound. Meanwhile, their in vitro antitumor activities were evaluated against SMMC-7721, MCF-7 and A549 human cancer cell lines by CCK-8 assay. The preliminary bioassay results demonstrated that all tested compounds 4a-q showed potent antitumor activities, and some compounds exhibited better effects than positive control ethaselen and 5-fluorouracil (5-FU) against various cancer cell lines. Furthermore, compounds 4b and 4m showed significant antitumor activities against SMMC-7721 cells with IC50 values of 1.89 and 1.89 μM, respectively. Compounds 4c and 4n displayed highly effective biological activities against MCF-7 cells with IC50 values of 2.88 and 2.28 μM, respectively. Compound 4i showed the best inhibitory effect against A549 cells with IC50 value of 1.76 μM. The pharmacological results suggest that the substituent groups of phenyl ring on the 1,3,4-thiadiazole are vital for modulating antitumor activities against various cancer cell lines.