2. Academic Validation
  3. Design, synthesis, and anticancer evaluation of benzophenone derivatives bearing naphthalene moiety as novel tubulin polymerization inhibitors

Design, synthesis, and anticancer evaluation of benzophenone derivatives bearing naphthalene moiety as novel tubulin polymerization inhibitors

  • Bioorg Chem. 2020 Nov;104:104265. doi: 10.1016/j.bioorg.2020.104265.
Guangcheng Wang 1,  Wenjing Liu 2,  Juan Tang 3,  Xue Ma 4,  Zipeng Gong 5,  Yong Huang 5,  Yongjun Li 4,  Zhiyun Peng 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: [email protected].
  • 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 The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
  • 4 Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China.
  • 5 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China.
  • 6 College of Food Science and Technology, Shanghai Ocean University, Shanghai, China. Electronic address: [email protected].
PMID: 32919128 DOI: 10.1016/j.bioorg.2020.104265
Abstract

A series of benzophenone derivatives bearing naphthalene moiety were designed, synthesized, characterized by 1H NMR, 13C NMR, and HRMS and evaluated for their antiproliferative activity against human breast Cancer cell line (MCF-7). Most of the tested derivatives showed good to moderate cytotoxicity against MCF-7 cell line. Among them, compound 4u (IC50 = 1.47 ± 0.14 μM) was found to be the most active compound, which is more active than the standard drug cisplatin (IC50 = 15.24 ± 1.27 μM). In vitro tubulin polymerization inhibition assay, EBI competition assay, cell cycle analysis, and cell Apoptosis assay identified that compound 4u was a new tubulin polymerization inhibitor by targeting the colchicine binding site. Besides, molecular docking study showed that compound 4u has high binding affinities with the colchicine binding site of tubulin through hydrogen bond, cation-π, and hydrophobic interaction.

Keywords

Anticancer activity; Benzophenone; Naphthalene; Tubulin polymerization inhibitors.

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