Synthesis and bioactive evaluation of N-((1-methyl-1 H-indol-3-yl)methyl)- N-(3,4,5-trimethoxyphenyl)acetamide derivatives as agents for inhibiting tubulin polymerization
- RSC Med Chem. 2022 Oct 28;14(1):113-121. doi: 10.1039/d2md00340f.
- 1. College of Chemistry and Chemical Engineering, Guangxi University Nanning 530004 China [email protected].
- 2. School of Basic Medicine, Guangxi Medical University Nanning 530021 China.
Based on the inhibitory effect of CA-4 analogues and indoles on tubulin polymerization, we designed and synthesized a series of N-((1-methyl-1H-indol-3-yl)methyl)-2-(1H-pyrazol-1-yl or triazolyl)-N-(3,4,5-trimethoxyphenyl)acetamides. All the synthesized compounds were evaluated for their in vitro antiproliferative activities against HeLa, MCF-7 and HT-29 Cancer cell lines, and some of the target compounds demonstrated effective activities towards the three tumour cell lines. Among them, compound 7d exhibited the most potent activities against HeLa (IC50 = 0.52 μM), MCF-7 (IC50 = 0.34 μM) and HT-29 (IC50 = 0.86 μM). Mechanistic studies revealed that compound 7d induced cell Apoptosis in a dose-dependent manner, arrested the cells in the G2/M phase and inhibited polymerization of tubulin via a consistent way with colchicine. Therefore, 7d is a potential agent for the further development of tubulin polymerization inhibitors.