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

  • Authors: Jin Y.1, Xin Y.2, Li Y.3, Chen X.4, Man D.5, Tian Y.1
  • Affiliations:
    1. Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy, Yanbian University
    2. Yanji, 133002, Jilin Province, Yanbian University
    3. Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy, Yanbian University,
    4. Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy,, Yanbian University
    5. Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy,, Yanbian University,
  • Issue: Vol 31, No 15 (2024)
  • Pages: 2090-2106
  • Section: Anti-Infectives and Infectious Diseases
  • URL: https://rjmseer.com/0929-8673/article/view/644415
  • DOI: https://doi.org/10.2174/0109298673263854231009063053
  • ID: 644415

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Full Text

Abstract

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

Methods: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. in vitro 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 (IC50 = 5.9 nM) and BEL-7402 (IC50 = 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 in vivo and in vitro and has the potential to be further developed into a highly effective antitumor agent with little toxicity to normal tissues.

About the authors

Ye-Zhi Jin

Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy, Yanbian University

Email: info@benthamscience.net

Ya-Bing Xin

Yanji, 133002, Jilin Province, Yanbian University

Email: info@benthamscience.net

Yuan Li

Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy, Yanbian University,

Email: info@benthamscience.net

Xin-Yuan Chen

Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy,, Yanbian University

Email: info@benthamscience.net

De-Ao Man

Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy,, Yanbian University,

Email: info@benthamscience.net

Yu-Shun Tian

Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy, Yanbian University

Author for correspondence.
Email: info@benthamscience.net

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