2. Academic Validation
  3. Design, synthesis and evaluation of structurally diverse chrysin-chromene-spirooxindole hybrids as anticancer agents

Design, synthesis and evaluation of structurally diverse chrysin-chromene-spirooxindole hybrids as anticancer agents

  • Bioorg Med Chem. 2019 Nov 15;27(22):115109. doi: 10.1016/j.bmc.2019.115109.
Wen-Hui Zhang 1,  Shuang Chen 1,  Xiong-Li Liu 2,  Ting-Ting Feng 3,  Wu-De Yang 3,  Ying Zhou 4
Affiliations

Affiliations

  • 1 Guizhou Medicine Edible Plant Resources Research and Development Center, Guizhou University, Guiyang 550025, China.
  • 2 Guizhou Medicine Edible Plant Resources Research and Development Center, Guizhou University, Guiyang 550025, China. Electronic address: xlliu1@gzu.edu.cn.
  • 3 College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
  • 4 College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China. Electronic address: yzhou@gzu.edu.cn.
PMID: 31615696 DOI: 10.1016/j.bmc.2019.115109
Abstract

A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro Anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC50 = 3.15 ± 0.51 μM), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the Apoptosis possibly through mitochondria-mediated Caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs.

Keywords

Anticancer agents; Chromene; Chrysin; Hybrids; Spirooxindole.

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