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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Disulfides
• 1,3,4-thiadiazole
• antiproliferative activity
• cytotoxicity
• phenacyl derivatives

Acknowledgements

We are grateful to the Tianjin Municipal Natural Science Foundation (18JCYBJC94900) and Training Project of Innovation Team of Colleges and Universities in Tianjin (TD13-5020) for financial support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Tianjin Natural Science Foundation: [Grant Number 18JCYBJC94900]; Training Project of Innovation Team of Colleges and Universities in Tianjin: [Grant Number TD13-5020].