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

• Published in: Bioorganic chemistry Vol. 103; pp. 104141 - 104149
• Main Authors: Wang, Guangcheng, Liu, Wenjing, Peng, Zhiyun, Huang, Yong, Gong, Zipeng, Li, Yongjun
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.10.2020; Elsevier
• Subjects: Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biochemistry & Molecular Biology; Cell Proliferation - drug effects; Chemistry; Chemistry, Organic; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Life Sciences & Biomedicine; MCF-7 Cells; Models, Molecular; Molecular Structure; Naphthalene; Naphthalenes - chemistry; Naphthalenes - pharmacology; Physical Sciences; Polymerization - drug effects; Pyrazole; Pyrazoles - chemistry; Pyrazoles - pharmacology; Science & Technology; Structure-Activity Relationship; Tubulin - metabolism; Tubulin polymerization inhibitor; Naphthalene; Anticancer; Tubulin polymerization inhibitor; Pyrazole; TARGET; CHALCONE DERIVATIVES; DOCKING
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104141

[Display omitted] •A novel series of pyrazole-naphthalene were designed and synthesized.•Anticancer activity was assessed against MCF-7 cell line.•Compound 5j inhibited tubulin polymerization.•Compound 5j arrested cell cycle at G2/M phase and induces apoptosis.•Molecular docking studies were performed. 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.