Design, synthesis, and screening for the antiproliferative activity of new 1,3,4-thiadiazole scaffold linked to substituted phenacyl derivatives and disulfides

Abstract

In the current research, twenty-eight new 1,3,4-thiadiazole scaffold linked to substituted phenacyl derivatives and disulfides were designed and synthesized, and Cell Counting Kit-8 (CCK-8) assay was used to detect their in vitro antiproliferative activities against human cancer cell lines SMMC-7721, Hela, A549 as well as normal mouse cell lines L929. The results showed that all the tested compounds 6a–g, chlorine derivatives 7a–g, nitro derivatives 8a–g and methyl derivatives 9a–g showed a certain degree of antiproliferative activity, and some compounds exhibited better antiproliferative activity against various cancer cells than the control drug 5-fluorouracil (5-FU). Among these, compound 6a showed the strongest inhibitory activity on SMMC-7721 cells with IC50 value of 1.62 µM. Compounds 6c, 7g, 8f and 8g displayed excellent antitumor activities against Hela cells with IC50 values of 3.65, 3.59, 3.71 and 3.21 µM, respectively. Compounds 6f, 7c and 7e revealed high antitumor activities against A549 cells with IC50 values of 3.22, 2.25 and 2.85 µM, respectively. Most of the compounds had relatively weak cytotoxicity to L929 cells.