Discovery of Novel Arylamide Derivatives Containing Piperazine Moiety As Inhibitors of Tubulin Polymerisation with Potent Liver Cancer Inhibitory Activity

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2023 Jul 25

PMID 37489043

Authors

Xiao-Yi Shi

Huang Jiao

Jia-Kai Zhang

Xin-Yi Tian

Dan-Feng Guo

Jie Gao

Mei-Qi Jia

Jian Song

Sai-Yang Zhang

Xiang-Jing Fu

Hong-Wei Tang

Affiliations

Soon will be listed here.

Abstract

In this work, a series of novel arylamide derivatives containing piperazine moiety were designed and synthesised as tubulin polymerisation inhibitors. Among 25 target compounds, compound () exhibited low nanomolar IC values ranging from 0.089 to 0.238 μM against nine human cancer cells. Its inhibitory effects on liver cancer cells were particularly evident with IC values of 89.42 and 91.62 nM for SMMC-7721 and HuH-7 cells, respectively. Further mechanism studies demonstrated that compound () could bind to the colchicine binding site of β-tubulin and directly act on β-tubulin, thus inhibiting tubulin polymerisation. Additionally, compound () could inhibit colony forming ability, cause morphological changes, block cell cycle arrest at the G2 phase, induce cell apoptosis, and regulate the expression of cell cycle and cell apoptosis related proteins in liver cancer cells. Overall, the promising bioactivities of compound () make the novel arylamide derivatives have the value for further development as tubulin polymerisation inhibitors with potent anticancer activities.

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