Anticancer and antibacterial activity in vitro evaluation of iridium(III) polypyridyl complexes

• Published in: Journal of biological inorganic chemistry 2019-03, Vol.24 (2), p.151-169
• Main Authors: Yi, Qiao-Yan, Zhang, Wen-Yao, He, Miao, Du, Fan, Wang, Xiu-Zhen, Wang, Yang-Jie, Gu, Yi-Ying, Bai, Lan, Liu, Yun-Jun
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antimicrobial activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Autophagy; Biochemistry; Biomedical and Life Sciences; Calcium (intracellular); Calcium (mitochondrial); Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Comet assay; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Cytochrome; Cytochrome c; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Escherichia coli - drug effects; Humans; Inorganic chemistry; Intracellular; Iridium - chemistry; Iridium - pharmacology; Life Sciences; Listeria monocytogenes - drug effects; Lysosomes; Membrane potential; Microbial Sensitivity Tests; Microbiology; Mitochondria; Molecular Structure; NMR; Nuclear magnetic resonance; Original Paper; Phagocytosis; Phenazopyridine - chemistry; Phenazopyridine - pharmacology; Polymerization; Salmonella - drug effects; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Triazine; Tubules
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-018-1635-8

Three iridium(III) polypyridyl complexes [Ir(ppy) 2 (PYTA)](PF 6 ) ( 1 ) (ppy = 2-phenylpyridine), [Ir(bzq) 2 (PYTA)](PF 6 ) ( 2 ) (bzq = benzo[h]quinolone) and [Ir(piq) 2 (PYTA)](PF 6 ) ( 3 ) (piq = 1-phenylisoquinoline, PYTA = 2,4-diamino-6-(2′-pyridyl)-1,3,5-triazine) were synthesized and characterized by elemental analysis, IR, 1 H NMR and 13 C NMR. The cytotoxic activity of the complexes toward cancer SGC-7901, Eca-109, A549, HeLa, HepG2, BEL-7402 and normal LO2 cell lines was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex 3 shows the most effective on inhibiting the above cell growth among these complexes. The complexes locate at the lysosomes and mitochondria. AO/EB, Annex V and PI and comet assays indicate that the complexes can induce apoptosis in SGC-7901 cells. Intracellular ROS and mitochondrial membrane potential were examined under fluorescence microscopy. The results demonstrate that the complexes increase the intracellular ROS levels and induce a decrease in the mitochondrial membrane potential. The complexes can enhance intracellular Ca 2+ concentration and cause a release of cytochrome c . The autophagy was studied using MDC staining and western blot. Complexes 1 – 3 can effectively inhibit the cell invasion with a concentration-dependent manner. Additionally, the complexes target tubules and inhibit the polymerization of tubules. The antimicrobial activity of the complexes against S. aureus , E. coli , Salmonella and L. monocytogenes was explored. The mechanism shows that the complexes induce apoptosis in SGC-7901 cells through ROS-mediated lysosomal–mitochondrial, targeting tubules and damage DNA pathways. Graphical Abstract Three iridium(III) complexes [Ir(N–C) 2 (PYTA)](PF 6 ) (N–C = ppy, 1 ; bzq, 2 ; piq, 3 ) were synthesized and characterized. The anticancer activity of the complexes against SGC-7901 cells was studied by apoptosis, comet assay, autophagy, ROS, mitochondrial membrane potential, intracellular Ca 2+ levels, release of cytochrome c , tubules and western blot analysis. The antibacterial activity in vitro was also assayed.