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New Organometallic Tetraphenylethylene⋅Iridium(III) Complexes with Antineoplastic Activity
Author(s) -
Liu Xicheng,
He Xiangdong,
Zhang Xiaojing,
Wang Yongling,
Liu Jiaying,
Hao Xiujuan,
Zhang Yue,
Yuan XiangAi,
Tian Laijin,
Liu Zhe
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900268
Subject(s) - iridium , chemistry , nad+ kinase , tetraphenylethylene , cisplatin , stereochemistry , nicotinamide , mechanism of action , nicotinamide adenine dinucleotide , combinatorial chemistry , medicinal chemistry , biochemistry , enzyme , catalysis , in vitro , fluorescence , biology , physics , chemotherapy , quantum mechanics , aggregation induced emission , genetics
Iridium(III) complexes have attracted more and more attention in the past few years because of their potential antineoplastic activity. In this study, four Ir III complexes of the types [(η 5 ‐Cp x )Ir(N^N)Cl]PF 6 (complexes 1 and 2 ) and [Ir(Phpy) 2 (N^N)]PF 6 (complexes 3 and 4 ) have been synthesized and characterized. They exhibit potential antineoplastic activity towards A549 cells, especially in the case of complex 1 [IC 50 =(3.56±0.5) μ m ], which was nearly six times as effective as cisplatin [(21.31±1.7) μ m ]. Additionally, these complexes show some selectivity towards cancer cells over normal cells. They could be transported by serum albumin (binding constants were changed from 0.37×10 5 to 81.71×10 5 m −1 ). Ir III complexes 1 and 2 could catalyze the transformation of nicotinamide adenine dinucleotide reduced form (NADH) into NAD + (turnover numbers 43.2, 11.9] and induce the accumulation of reactive oxygen species, thus confirming their antineoplastic mechanism of oxidation, whereas the cyclometalated complexes 3 and 4 were able to target the lysosome [Pearson co‐localization coefficient (PCC)=0.73], cause lysosomal damage, and induce apoptosis. Understanding the mechanism of action would help further structure–activity optimization on these Ir III complexes as emerging cancer therapeutics.