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

Autor:	Xie-Er Jian, Fang Yang, Lin Chen, Yu-Feng Ma, Pei-Liang Zhao, You Wenwei, Yu-Xia Liu
Rok vydání:	2021
Předmět:	Indole test biology 1 2 4-Triazole General Chemistry Cell cycle biology.organism_classification Catalysis HeLa chemistry.chemical_compound Tubulin Biochemistry chemistry Apoptosis Materials Chemistry biology.protein Cytotoxic T cell IC50
Zdroj:	New Journal of Chemistry. 45:21869-21880
ISSN:	1369-9261 1144-0546
DOI:	10.1039/d1nj03892c
Popis:	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 μM) toward HEK-293, a normal human embryonic kidney cell line. Mechanism analysis indicated that 9p significantly arrested cell cycle at G2/M phase and induced apoptosis in HeLa cells with a dose-dependent manner. Further evidence demonstrated that the promising compound effectively inhibited tubulin polymerization with the IC50 value of 8.3 μM, and molecular docking studies revealed that 9p well occupied the colchicine-site in tubulin. The present study highlighted that indole-triazole hybrids might be used as the promising scaffold to develop novel tubulin polymerization inhibitors for cancer treatment.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::2d3871863b145bc8cf4180e85745ab03 https://doi.org/10.1039/d1nj03892c Zobrazit plný text záznamu