Discovery of new indole-based 1,2,4-triazole derivatives as potent tubulin polymerization inhibitors with anticancer activity

Thirty-six novel indole-based 1,2,4-triazole derivatives were designed and synthesized through the molecular hybrid strategy. The bioassay results revealed that 9p displayed excellent antiproliferative efficacies in the nanomolar range against HeLa cells. Importantly, the compound exhibited no obvious cytotoxic activity (IC50 > 100 mu M) toward HEK-293, a normal human embryonic kidney cell line. Mechanism analysis indicated that 9p significantly arrested the cell cycle at the G2/M phase and induced apoptosis in HeLa cells in a dose-dependent manner. Further evidence demonstrated that the promising compound effectively inhibited tubulin polymerization with an IC50 value of 8.3 mu M, and molecular docking studies revealed that 9p well occupied the colchicine-site in tubulin. The present study highlights that indole-triazole hybrids might be used as a promising scaffold to develop novel tubulin polymerization inhibitors for cancer treatment.

Automated summary

A series of novel indole-based 1,2,4-triazole derivatives were designed and synthesized, with compound 9p showing excellent antiproliferative efficacy against HeLa cells in the nanomolar range and no cytotoxic activity towards normal cells. Mechanism analysis revealed that 9p arrested the cell cycle and induced apoptosis in HeLa cells, while also effectively inhibiting tubulin polymerization. The study suggests that indole-triazole hybrids could serve as a promising scaffold for developing novel tubulin polymerization inhibitors for cancer treatment.