title: Synthesis and in vitro antitumor activity of novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands.
abstract: Four novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands were designed, synthesized, and characterized by FT-IR, NMR, and MS. The cytotoxicities of all of the complexes against the human solid tumor cell lines A2780, A549, KB, and MDA-MB-231 were evaluated. Both R,R-configured complexes (R,R)-5a and (R,R)-5b exhibited more potent or similar activity compared with oxaliplatin, whereas their corresponding (S,S)-isomers (S,S)-5a and (S,S)-5b were found to be mostly inactive. As indicated by the activation of caspase-3, the cleavage of PARP, and the upregulation of p53, the preliminary mechanism studies revealed that the mode of cell death initiated by (R,R)-5a in A2780 cells was predominantly p53-mediated apoptosis. In addition, the structure of (R,R)-5a was unambiguously confirmed through single crystal X-ray structure determination.
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Jiao
authors.initials: J
authors.lastname: Song
authors.forename: Meng-Ting
authors.initials: MT
authors.lastname: Qian
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Yu
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007495:Iridium / Q000737:chemistry* / Q000494:pharmacology*; D007536:Isomerism; D008024:Ligands
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003959:Diamines; D008024:Ligands; D007495:Iridium
keywords: C(2)-Symmetrical; Cytotoxicity; Enantiopure vicinal diamine; Iridium(III) complexes