Novel hybrid molecules based on disulfides and 1,2,4-triazole as antiproliferative agents

Abstract

A series of novel hybrid molecules based on disulfides and 1,2,4-triazole were synthesized, and the structures of the resulting compounds (7a–7g, 8a–8g and 9a–9g) were confirmed by their IR, ¹H NMR, ¹³C NMR and HR-ESI-MS spectroscopic data. The in vitro antiproliferative activity of the tested compounds on human cancer cells A549, Hela, SMMC-7721, and normal cells L929 was determined by CCK-8 assay. The obtained data revealed that most of the tested compounds showed some degrees of antiproliferative activity, and some compounds displayed better effects than positive control 5-FU against various cancer cells. Especially, 3-phenyl-5-(n- butyldisulfanyl)-1,2,4-triazole（7c）exhibited highly effective antitumor activity against A549 cells with IC₅₀ value of 3.55 μM. 3-(4-methoxyphenyl)-5-(n-hexyldisulfanyl) −1,2,4-triazole （9 g） was found to have the best inhibitory effect on Hela cells with IC₅₀ value of 3.46 μM. 3-phenyl-5-(2-butyldisulfanyl)-1,2,4-triazole（7e）showed the greatest inhibitory activity on SMMC-7721 cells with IC₅₀ value of 1.08 μM. In addition, all compounds exhibited weaker cytotoxic effects than 5-FU on L929 cells.

Graphical Abstract

Keywords:

• Disulfide;1,2,4-triazole
• antiproliferative activity
• cytotoxicity

Conflicts of interest

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the Tianjin Natural Science Foundation (18JCYBJC94900) and Training Project of Innovation Team of Colleges and Universities in Tianjin (TD13-5020).