title: 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 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.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
authors.forename: Gui-yang
authors.initials: GY
authors.lastname: Yao
authors.forename: Man-yi
authors.initials: MY
authors.lastname: Ye
authors.forename: Ri-zhen
authors.initials: RZ
authors.lastname: Huang
authors.forename: Ya-jun
authors.initials: YJ
authors.lastname: Li
authors.forename: Yong-tao
authors.initials: YT
authors.lastname: Zhu
authors.forename: Ying-ming
authors.initials: YM
authors.lastname: Pan
authors.forename: Zhi-xin
authors.initials: ZX
authors.lastname: Liao
authors.forename: Heng-shan
authors.initials: HS
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013237:Stereoisomerism; D014315:Triterpenes / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D007094:Imides; D014315:Triterpenes; C027815:maleopimaric acid
keywords: Apoptosis; Atropisomers; Cytotoxicity; Diimides; Maleopimaric acid