Synthesis, antitumor and antimicrobial evaluation of novel 1,3,4-thiadiazole derivatives bearing disulfide bond

Abstract

In the present study, the synthesis of novel 1,3,4-thiadiazole derivatives bearing disulfide bond are accomplished in good yields with employing a convergent synthetic route, and their in vitro antiproliferative activities were screened against human cancer cell lines A549, Hela, SMMC-7721, and normal cell lines L929 by CCK-8 assay. Meanwhile, all compounds were evaluated for their in vitro antimicrobial activities against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus strains. Screening results indicated that some of the tested compounds 6a–6h, 7a–7h, and 8a–8h possessed better antiproliferative activity than positive control 5-fluorouracil. Compounds 7f, 7h, and 8h displayed significant antitumor activities against SMMC-7721 cells with IC50 values 2.37, 3.80, and 2.72 µM, respectively. Compounds 6g, 7g, 7h, and 8g showed great antitumor effects against Hela cells with IC50 values 1.29, 2.56, 3.43, and 2.14 µM, respectively. Compounds 6e, 8a, and 8h exhibited highly effective antiproliferative activities against A549 cells with IC50 values 3.43, 2.12, and 3.81 µM, respectively. Most of tested compounds exerted weak cytotoxic effects on normal human cell line L929. Biological evaluation indicated that all the tested compounds possessed antimicrobial activity with certain degrees.