Design, synthesis, antiproliferative and antimicrobial evaluation of a new class of disulfides containing 1,3,4-thiadiazole units

In the present study, 24 kinds of 2-arylamino-5-substituteddisulfanyl-1,3,4-thiadiazoles were prepared through multistep synthesis. The structures of synthesized compounds were confirmed by their IR, H-1 NMR, C-13 NMR, and HR-ESI-MS spectroscopic data. The inhibitory activity of all the target compounds was determined toward three human cancer cell lines including SMMC-7721, A549, Hela, and the normal cell line 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. The obtained data revealed that all the tested compounds showed some degrees of antiproliferative activity, and some compounds displayed better effects than reference drugs 5-FU and PX-12 against various cancer cells. Especially, compounds 8c, 8e, and 8f exhibited excellent growth inhibitory effect against SMMC-7721 cells with the IC50 values of 3.22, 3.21, and 2.86 mu M, respectively. Compound 8e displayed the greatest inhibitory activity against A549 cells with IC50 value of 4.29 mu M. Compounds 8a was found to have the most potent antitumor activity against Hela cells with IC50 value 3.59 mu M. Reactive oxygen species (ROS) assay shows that after treated with some target compounds, cellular ROS were significantly increased. Furthermore, all compounds exhibited weaker cytotoxic effects than 5-FU and PX-12 on L929 cells. In general, the above preliminary observations suggested that this class of disulfide derivatives could serve as promising molecular templates in searching for antitumor agent with satisfactory therapeutic effect. The biological evaluation indicated that all the tested compounds possessed antimicrobial activity with certain degrees. [GRAPHICS] .