Synthesis, biological evaluation, and molecular modelling of new naphthalene-chalcone derivatives as potential anticancer agents on MCF-7 breast cancer cells by targeting tubulin colchicine binding site

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 35; no. 1; pp. 139 - 144
• Main Authors: Wang, Guangcheng, Liu, Wenjing, Gong, Zipeng, Huang, Yong, Li, Yongjun, Peng, Zhiyun
• Format: Journal Article
• Language: English
• Published: ABINGDON Taylor & Francis 01.01.2020; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Apoptosis; Apoptosis - drug effects; Binding sites; Binding Sites - drug effects; Biochemistry & Molecular Biology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Proliferation - drug effects; Chalcone; Chalcones - chemistry; Chalcones - pharmacology; Chemistry, Medicinal; Cisplatin; Colchicine; Colchicine - antagonists & inhibitors; Colchicine - metabolism; Cytotoxicity; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Life Sciences & Biomedicine; MCF-7 Cells; Models, Molecular; Molecular modelling; Molecular Structure; Naphthalene; Naphthalenes - chemistry; Naphthalenes - pharmacology; Pharmacology & Pharmacy; Polymerization; Rapid Communication; Science & Technology; Short Communication; Structure-Activity Relationship; synthesis; Tubulin; Tubulin - metabolism; tubulin inhibitor; Tubulin Modulators - chemical synthesis; Tubulin Modulators - chemistry; Tubulin Modulators - pharmacology; Tumors; synthesis; tubulin inhibitor; CYCLE ARREST; POLYMERIZATION INHIBITORS; CYTOTOXIC ACTIVITY; Chalcone; anticancer; DISCOVERY
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2019.1690479

A series of naphthalene-chalcone derivatives (3a-3t) were prepared and evaluated as tubulin polymerisation inhibitor for the treatment of breast cancer. All compounds were evaluated for their antiproliferative activity against MCF-7 cell line. The most of compounds displayed potent antiproliferative activity. Among them, compound 3a displayed the most potent antiproliferative activity with an IC 50 value of 1.42 ± 0.15 µM, as compared to cisplatin (IC 50  = 15.24 ± 1.27 µM). Additionally, the promising compound 3a demonstrated relatively lower cytotoxicity on normal cell line (HEK293) compared to tumour cell line. Furthermore, compound 3a was found to induce significant cell cycle arrest at the G 2 /M phase and cell apoptosis. Compound 3a displayed potent tubulin polymerisation inhibitory activity with an IC 50 value of 8.4 µM, which was slightly more active than the reference compound colchicine (IC 50  = 10.6 µM). Molecular docking analysis suggested that 3a interact and bind at the colchicine binding site of the tubulin.