Affiliation:
1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510006 P R China
2. Center for Mitochondrial Biology and Medicine The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology and Frontier Institute of Science and Technology Xi'an Jiaotong University Xi An Shi Xi'an 710049 P. R. China
Abstract
AbstractTwo novel unsymmetrical Ir(III) complexes [Ir(ppy)2(N N)Cl2] (N N=2‐(pyrazin‐2‐yl)naphtha[1,2‐e][1,2,4]triazine,Ir1; 2‐(pyrazin‐2‐yl)‐4b,4b’‐dihydroaceanthryleno[1,2‐e][1,2,4]triazine,Ir2) were developed as chemotherapy agents.Ir1was mainly located in mitochondria. In contrast,Ir2accumulated in mitochondria but subsequently migrated to the nucleus.Ir1andIr2showed cytotoxicity toward cancerous cells, especially the cisplatin‐resistant ones, indicating their ability to overcome cisplatin resistance. Although bothIr1andIr2disrupted mitochondrial metabolism, they showed different cell death mechanisms.Ir1induced mitochondria‐mediated apoptosis in cisplatin‐resistant A549R cells.Ir2was demonstrated to cause PARP‐1 activated necroptosis in A549R cells. This study provides an experimental basis for the rational design of metal‐based chemotherapeutic drugs.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province for Distinguished Young Scholars
Cited by
2 articles.
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