The Effect of 1,2,4-Triazole-3-thiol Derivatives Bearing Hydrazone Moiety on Cancer Cell Migration and Growth of Melanoma, Breast, and Pancreatic Cancer Spheroids

4-Phenyl-3-[2-(phenylamino)ethyl]-1H-1,2,4-triazole-5(4H)-thione was used as a starting compound for the synthesis of the corresponding 1,2,4-triazol-3-ylthioacetohydrazide, which reacts with isatins and various aldehydes bearing aromatic and heterocyclic moieties provided target hydrazones. Their cytotoxicity was tested by the MTT assay against human melanoma IGR39, human triple-negative breast cancer (MDA-MB-231), and pancreatic carcinoma (Panc-1) cell lines. The selectivity of compounds towards cancer cells was also studied. In general, the synthesized compounds were more cytotoxic against the melanoma cell line. N0 -(2-oxoindolin-3-ylidene)-2-((4-phenyl-5(2-(phenylamino)ethyl)-4H-1,2,4-triazol-3-yl)thio)acetohydrazide, N0 -((1H-pyrrol-2-yl)methylene)2-((4-phenyl-5-(2-(phenylamino)ethyl)-4H-1,2,4-triazol-3-yl)thio)acetohydrazide and N0-(2-hydroxy-5nitrobenzylidene)-2-((4-phenyl-5-(2-(phenylamino)ethyl)-4H-1,2,4-triazol-3-yl)thio)acetohydrazide were identified as the most active among all synthesized compounds in 3D cell cultures. N0 (4-(dimethylamino) benzylidene)-2-((4-phenyl-5-(2-(phenylamino)ethyl)-4H-1,2,4-triazol-3-yl)thio) acetohydrazide inhibited all cancer cell migration, was characterized as relatively more selective towards cancer cells, and could be further tested as an antimetastatic candidate.

Automated summary

This study synthesized various compounds and tested their cytotoxicity against different cancer cell lines, with some compounds showing strong toxicity against melanoma cells. Some of these compounds exhibited the most active anti-cancer activity in 3D cell cultures.