Synthesis and Selective Anticancer Activity Evaluation of 2-phenylacrylonitrile Derivatives As Tubulin Inhibitors

Overview

Journal Curr Med Chem

Publisher Bentham Science Publishers

Specialty Chemistry

Date 2024 Feb 22

PMID 38384112

Authors

Ye-Zhi Jin

Ya-Bing Xin

Yuan Li

Xin-Yuan Chen

De-Ao Man

Yu-Shun Tian

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed at synthesizing 13 series of novel derivatives with 2-phenylacrylonitrile, evaluating antitumor activity both and , and obtaining novel tubulin inhibitors.

Method: The 13 series of 2-phenylacrylonitrile derivatives were synthesized by Knoevenagel condensation and the anti-proliferative activities were determined by MTT assay. The cell cycle and apoptosis were analyzed by flow cytometer. Quantitative cell migration was performed using 24-well Boyden chambers. The proteins were detected by western blotting. kinetics of microtubule assembly was measured using ELISA kit for Human β-tubulin (TUBB). Molecular docking was done by Discovery Studio (DS) 2017 Client online tool.

Results: Among the derivatives, compound 1g2a possessed strong inhibitory activity against HCT116 (IC = 5.9 nM) and BEL-7402 (IC = 7.8 nM) cells. Compound 1g2a exhibited better selective antiproliferative activities and specificities than all the positive control drugs, including taxol. Compound 1g2a inhibited proliferation of HCT116 and BEL-7402 cells by arresting them in the G2/M phase of the cell cycle, inhibited the migration of HCT116 and BEL-7402 cells and the formation of cell colonies. Compound 1g2a showed excellent tubulin polymerization inhibitory activity on HCT116 and BEL-7402 cells. The results of molecular docking analyses showed that 1g2a may inhibit tubulin to exert anticancer effects.

Conclusion: Compound 1g2a shows outstanding antitumor activity both and and has the potential to be further developed into a highly effective antitumor agent with little toxicity to normal tissues.

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