Synthesis and antitumor activity evaluation of maleopimaric acid N-aryl imide atropisomers

  • Bioorg Med Chem Lett. 2013 Dec 15;23(24):6755-8. doi: 10.1016/j.bmcl.2013.10.028.
Gui-yang Yao  1 ,  Man-yi Ye ,  Ri-zhen Huang ,  Ya-jun Li ,  Yong-tao Zhu ,  Ying-ming Pan ,  Zhi-xin Liao ,  Heng-shan Wang
Affiliations
  • 1. Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
PMID: 24211021 DOI: 10.1016/j.bmcl.2013.10.028
Abstract

Maleopimaric acid N-aryl imides (2) and methyl maleopimaric acid N-aryl imides (3) were designed and synthesized. Their atropisomers (A and B) were separated into their enantiomeric pure forms and the anti-proliferative activity was tested against NCI, A549, Hep G-2, MGC-803 and Hct-116 cell lines, respectively. A significant difference in the level of cytotoxicity was observed between R and S conformers. Atropisomers A with an R configuration exhibited significant toxicity (the IC50 values ranging from 7.51 to 32.1 μM). Further experiments proved that antitumor activity of 2A was achieved through the induction of cell Apoptosis by G1 cell-cycle arrest.

Keywords
Apoptosis; Atropisomers; Cytotoxicity; Diimides; Maleopimaric acid.