Cyclometalated iridium(III) complexes as mitochondria-targeted anticancer and antibacterial agents to induce both autophagy and apoptosis.

Autor: Chen BB; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China; Pharmacy Department, The People's Hospital of Gaozhou, Maoming 525200, China., Pan NL; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China., Liao JX; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China., Huang MY; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China., Jiang DC; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China., Wang JJ; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China., Qiu HJ; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China., Chen JX; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China. Electronic address: cppcc@qq.com., Li L; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China., Sun J; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China. Electronic address: sunjing03@foxmail.com.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2021 Jun; Vol. 219, pp. 111450. Date of Electronic Publication: 2021 Mar 29.
DOI: 10.1016/j.jinorgbio.2021.111450
Abstrakt: Mitochondrial damage will hinder the energy production of cells and produce excessive ROS (reactive oxygen species), resulting in cell death through autophagy or apoptosis. In this paper, four cyclometalated iridium(III) complexes (Ir1: [Ir(piq) 2 L]PF 6 ; Ir2: [Ir(bzq) 2 L]PF 6 ; Ir3: [Ir(dfppy) 2 L]PF 6 ; Ir4: [Ir(thpy) 2 L]PF 6 ; piq = 1-phenylisoquinoline; bzq = benzo[h]quinoline; dfppy = 2-(2,4-difluorophenyl)pyridine;thpy = 2-(2-thienyl)pyridine; L = 1,10-phenanthroline-5-amine) were synthesized and characterized. Cytotoxicity tests show that these complexes have excellent cytotoxicity to cancer cells, and mechanism studies indicatethat these complexes can specifically target mitochondria. Complexes Ir1 and Ir2 can damage the function of mitochondria, subsequently increasing intracellular levels of ROS, decreasing MMP (mitochondrial membrane potential), and interfering with ATP energy production, which leads to autophagy and apoptosis. Furthermore, autophagy induced by Ir1 and Ir2 can promote cell death in coordination with apoptosis. Surprisingly, these four complexes also showed moderate antibacterial activity to S. aureusand P. aeruginosa.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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