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

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 IC 50 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.