Syntheses and bioactivities of iridium(Ⅲ)complexes containing modified α-lipoic acid ligand as poten

• 作 者: Mengmeng Wang Yaqiong Kong Zhi Su Hongke Liu
• 机 构: School of Chemistry and Materials Science,Nanjing Normal University,Nanjing,210023
• 出 处: 第十一届全国化学生物学学术会议
• 发表日期: 2019年3期
• 关键词: Iridium complex α-Lipoic acid derivative Anticancer

　　Half-sandwich and cyclometalated metal-based anticancer agents have great distinction in their mechanisms of actions(MoAs)[1-2].To further understand the MoAs,two Ir(Ⅲ)complexes with the modified α-lipoic acid(N^N-LA),named Ir1 and Ir2,have been synthesized,where Ir1 owns the half-sandwich structure with the formula of [Ir(Cp*)(N^N-LA)Cl]PF6(Cp* = 1,2,3,4,5-pentamethyl-cyclopentadiene)and Ir2 indicates the cyclometalated structure with the formula of [Ir(C^N)2(N^N-LA)]PF6(C^N = 2-phenylpyridine).Both Ir1 and Ir2 have shown the ability to bind to BSA with the binding constants of 1.10×105 M-1 and 3.69×104 M-1,respectively,while Ir2 showed more binding sites than Ir1.Ir1 has shown no cytotoxicity to all tested cancer cell lines(Table 1),which may be due to the low lipophilicity for hard penetration to the cancer cells,the easy hydroxylation and reaction with GSH before reaching the targets.Ir2,however,has exhibited promising cytotoxicity towards to diverse cancer cell lines in vitro(Table 1).The mechanism of Ir2 interaction with A549 cells has been investigated,which could localize and accumulate in the lysosomes of A549 cells,generate ROS,arrest the cycle at G0/G1 and lead to the cell death by autophagy instead of apoptosis.This study for the half-sandwich and cyclometalated metal-based anticancer agents has highlighted the different MoAs towards the cancer cells and provided a new insight for understanding the structure-property relationships.