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
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Affiliations:
- Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy, Yanbian University
- Yanji, 133002, Jilin Province, Yanbian University
- Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy, Yanbian University,
- Key Laboratory of Natural Medicines of the Changbai Mountain, Department of Medicinal Chemistry, Ministry of Education, College of Pharmacy,, Yanbian University
- 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://hum-ecol.ru/0929-8673/article/view/644415
- DOI: https://doi.org/10.2174/0109298673263854231009063053
- ID: 644415
Cite item
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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