Synthesis, Characterisation of New Indolyl-1,2,4-triazole Derivatives and their Synergistic Anticancer Activity with Adriamycin against MCF-7 Cells

Abstract

A series of novel indolyl-1,2,4-triazole derivatives 7a-l were synthesised through a multistep pathway starting from 2-methyl-4-substituted anilines. Initial formylation furnished the corresponding indole precursors, which were further transformed into 5-substituted indoles and subsequently N-alkylated to yield 1,5-disubstituted-1H-indoles. These intermediates were converted into the corresponding indole-3-carbonitriles, which underwent cyclocondensation with appropriate acid hydrazides to provide the target indolyltriazole frameworks. Following this, the in vitro cytotoxicity of the synthesised derivatives 7a-l was assessed in breast cancer at the cellular level on the MCF-7 cell line. Some of the synthesised derivatives showed excellent to good inhibitory activity with GI₅₀ < 10 to 52.9 µg/mL when compared to the standard drug Adriamycin (GI₅₀ < 10 µg/mL). Significant suppression of cell growth was observed by compounds 7h-k, which exhibited 50% inhibition of cell growth at a concentration of less than 10 µg/mL, suggesting their potential as a therapeutic agent against breast cancer. The synergistic potential of the most active compound 7k was evaluated in combination with adriamycin and the combination exhibited significantly higher cytotoxicity against the MCF-7 cell line than compound 7k alone.