Biological evaluation of new mimetics of annonaceous acetogenins: alteration of right scaffold by click linkage with aromatic functionalities

  • Eur J Med Chem. 2014 May 6:78:248-58. doi: 10.1016/j.ejmech.2014.03.062.
Yanghan Liu  1 ,  Qicai Xiao  1 ,  Yongqiang Liu  2 ,  Zheng Li  3 ,  Yatao Qiu  1 ,  Guang-Biao Zhou  4 ,  Zhu-Jun Yao  5 ,  Sheng Jiang  6
Affiliations
  • 1. Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
  • 2. Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 3. Department of Translational Imaging, The Houston Methodist Research Institute, Houston, TX 77030, United States.
  • 4. Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: [email protected].
  • 5. State Key Laboratory of Coordination Chemistry, Nanjing National Laboratory of Microstructures, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093, China. Electronic address: [email protected].
  • 6. Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: [email protected].
PMID: 24686011 DOI: 10.1016/j.ejmech.2014.03.062
Abstract

A small library of analogues of annonaceous acetogenins through click linkage with aromatic moieties is established using a convergent modular fragment-assembly approach. These analogues exhibited low micromolar inhibitory activities against the proliferation of several human Cancer cell lines. Structure-activity relationship (SAR) of these analogues indicates that replacement of the methoxy groups of ubiquinone ring with methyl groups is proved to be a useful strategy for improving the Anticancer activity of quinone-acetogenin hybrids.

Keywords
Annonaceous acetogenins; Aromatic functionalities; Click chemistry; Cytotoxicity; Quinone.