Synthesis, , Evaluation of Furanyl- and Thiophenyl-3-phenyl-1-indole-2-carbohydrazide Derivatives As Tubulin Inhibitors and Anticancer Agents

Overview

Journal RSC Med Chem

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Jul 19

PMID 39026641

Authors

Rungroj Saruengkhanphasit

Lukana Ngiwsara

Kriengsak Lirdprapamongkol

Jaruwan Chatwichien

Worawat Niwetmarin

Chatchakorn Eurtivong

Prasat Kittakoop

Jisnuson Svasti

Somsak Ruchirawat

Affiliations

Soon will be listed here.

Abstract

Twenty-one new indole derivatives comprising of seven furanyl-3-phenyl-1-indole-carbohydrazide derivatives and fourteen thiophenyl-3-phenyl-1-indole-carbohydrazide derivatives were synthesised and biologically evaluated for their microtubule-destabilising effects, and antiproliferative activities against the National Cancer Institute 60 (NCI60) human cancer cell line panel. Among the derivatives, 6i showed the best cytotoxic activity exhibiting selectivity for COLO 205 colon cancer (LC = 71 nM), SK-MEL-5 melanoma cells (LC = 75 nM), and MDA-MB-435 (LC = 259 nM). Derivative 6j showed the strongest microtubule-destabilising effect. Both 6i and 6j were able to induce G2/M cell cycle arrest and apoptosis in MDA-MB-231 triple-negative breast cancer cells. Molecular docking simulation results suggested that these derivatives inhibit tubulin by binding at the colchicine site. The calculated molecular descriptors showed that the most potent derivatives have acceptable pharmacokinetic profiles and are favourable for oral drug administration.

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