2. Academic Validation
  3. Synthesis and biological evaluation of novel chalcone derivatives as a new class of microtubule destabilizing agents

Synthesis and biological evaluation of novel chalcone derivatives as a new class of microtubule destabilizing agents

  • Eur J Med Chem. 2017 May 26:132:11-25. doi: 10.1016/j.ejmech.2017.03.031.
Xiaochao Huang 1,  Rizhen Huang 1,  Lingxue Li 1,  Shaohua Gou 2,  Hengshan Wang 3
Affiliations

Affiliations

  • 1 Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.
  • 2 Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China. Electronic address: sgou@seu.edu.cn.
  • 3 State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, China. Electronic address: whengshan@163.com.
PMID: 28340411 DOI: 10.1016/j.ejmech.2017.03.031
Abstract

A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human Cancer lines, with the IC50 values ranged from 3.75 to 8.42 μM. In addition, compound 12k was found to induce Apoptosis in NCI-H460 cells via the mitochondrial pathway, including an increase of the ROS level, loss of mitochondrial membrane potential, release of cytochrome c, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase-9 and Caspase-3, respectively. Moreover, the cell cycle analysis indicated that 12k effectively caused cell cycle arrest at G2/M phase. The results of tubulin polymerization assay displayed that 12k could inhibit tubulin polymerization in vitro. Furthermore, molecular docking study indicated that 12k can be binding to the colchicine site of tubulin.

Keywords

Anti-tumor activity; Apoptosis; Chalcone; Molecular modeling; Tubulin.

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