Cyclometalated Iridium-Nitrone Complexes Activated By C-H Bond As Anti-Proliferative A Gents And Its Preliminary Pharmacological Studies

Cancer has become one of the most severe threats to human health.There are so many measures to treat cancer,surgical treatment,radiotherapy,chemotherapy,and biological therapy et.al.The most widely used measure is chemotherapy.Since Barnett Rosenberg discovered that cisplatin could prevent tumor growth and inhibit metastasis progression in 1964,plenty of cisplatin analogs and other metal-based drugs have been selected as potential anticancer agents.Researches on other metal-based anticancer agents have increased in the decades.But the side effects and drug resistance of these agents have limited clinical practices.Previously our group have researched a series of iridium hydride complexes activated by C-H Bonds with PBN（N-tert-Butyl-α-nitrone）as its ligand,which had excellent antitumor activity and low drug toxicity.Based on this work,we present here,the design,synthesis,spectroscopic characterization,and in vitro biological assessment of six kinds of new iridium-nitrone complexes with free nitrone ligand.We detected the spectral characteristics of all complexes.The X-ray structures of compound 2a and 3b were reported.We also demonstrated that compound 2a was stable in water,air and microsomes via HLPC.All complexes have anticancer activity towards Hela、MCF-7、HepG₂、A549 and A2780 except the corresponding ligands.Compound 2a was the most active toward A2780 human ovarian cancer cells with the IC50 which was 0.49±0.042uM,and more active than cispltain about 60 times.This might be attributed to acetone ligand,PBN containing isopropyl and a free nitrone group in the structure.Compound 2a could induce cell apoptosis via Annexin V-PI apoptosis detection kit.Preliminary studies showed that one of the apoptosis mechanism of compound 2a was induced by the generation of ROS in A2780 cells,and might also react with C and G nulelbases.Our work indicated that this new type of iridium complexes with a free nitone ligand could be a possible alternative for further evaluation as anti-proliferative drugs for human cancers.