title: Activation of C-H bonds in nitrones leads to iridium hydrides with antitumor activity.
abstract: We report the design and synthesis of a series of new cyclometalated iridium hydrides derived from the C-H bond activation of aromatic nitrones and the biological evaluation of these iridium hydrides as antitumor agents. The nitrone ligands are based on the structure of a popular antioxidant, α-phenyl-N-tert-butylnitrone (PBN). Compared to cisplatin, the iridium hydrides exhibit excellent antitumor activity on HepG2 cells. The metal-coordinated compound with the most potent anticancer activity, 2f, was selected for further analysis because of its ability to induce apoptosis and interact with DNA. During in vitro studies and in vivo efficacy analysis with tumor xenograft models in Institute of Cancer Research (ICR) mice, complex 2f exhibited antitumor activity that was markedly superior to that of cisplatin. Our results suggest, for the first time, that metal hydrides could be a new type of metal-based antitumor agent.
authors.affiliation: Institute of Chemistry and BioMedical Sciences, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Song
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Rong
authors.initials: R
authors.lastname: Ben
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D007495:Iridium / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D009589:Nitrogen Oxides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009589:Nitrogen Oxides; C015388:nitrones; D007495:Iridium; D002244:Carbon; D006859:Hydrogen