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  3. Design, synthesis, molecular modeling, and biological evaluation of pyrazole-naphthalene derivatives as potential anticancer agents on MCF-7 breast cancer cells by inhibiting tubulin polymerization

Design, synthesis, molecular modeling, and biological evaluation of pyrazole-naphthalene derivatives as potential anticancer agents on MCF-7 breast cancer cells by inhibiting tubulin polymerization

  • Bioorg Chem. 2020 Oct;103:104141. doi: 10.1016/j.bioorg.2020.104141.
Guangcheng Wang 1,  Wenjing Liu 2,  Zhiyun Peng 3,  Yong Huang 4,  Zipeng Gong 5,  Yongjun Li 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; College of Chemistry and Chemical Engineering, Jishou University, Jishou, China. Electronic address: wanggch123@163.com.
  • 2 Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China; School of Pharmacy, Guizhou Medical University, Guiyang, China.
  • 3 College of Food Science and Technology, Shanghai Ocean University, Shanghai, China. Electronic address: pengzhiyun1986@163.com.
  • 4 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China.
  • 5 Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China.
  • 6 Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China. Electronic address: liyongjun026@126.com.
PMID: 32750611 DOI: 10.1016/j.bioorg.2020.104141
Abstract

A new series of pyrazole-naphthalene derivatives (5a-5q) have been synthesized and evaluated for their Anticancer activity against human breast Cancer cell lines (MCF-7). Most of newly synthesized compounds (except 5i, 5m, and 5p) exhibited potent antiproliferative activity in the range of IC50 = 2.78 ± 0.24 μM - 9.13 ± 0.47 μM. Among them, compound 5j (IC50 = 2.78 ± 0.24 μM), bearing ethoxy at the 4-position of the phenyl ring, was found to be the most active compound in this series of compounds, with five folds more active than the standard drug cisplatin (IC50 = 15.24 ± 1.27 μM). In addition, compound 5j and colchicine showed the same ability to inhibit tubulin polymerization with the IC50 values of 4.6 μM and 6.7 μM, respectively. Cellular mechanism studies elucidated that compound 5j arrested the cell cycle at G2/M phase and induced Apoptosis. Furthermore, molecular docking analysis revealed that compound 5j formed stable interactions in the colchicine-binding site of tubulin.

Keywords

Anticancer; Naphthalene; Pyrazole; Tubulin polymerization inhibitor.

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