title: Designing new iridium(iii) arene complexes of naphthoquinone derivatives as anticancer agents: a structure-activity relationship study.
abstract: A series of iridium(iii) arene complexes of naphthoquinone derivatives of the formula [IrIII(η6-L1)(L2)(3,5-(NO2)2pcyd)](PF6) (L1 = p-methylphenyl)ethynylferrocene; L2 = Lap: lapachol, 1, Plum: plumbagin, 2, Law: lawsone, 3, and Jug: juglone, 4; 3,5-(NO2)2pcyd = 3,5-dinitrophenylcyanamide) have been synthesized and investigated for their suitability as potential anticancer drugs. The DNA-binding interactions of the complexes with calf thymus DNA have been studied by absorption, emission, and viscosity measurements. Their cytotoxicity against the cancer cell lines including colon adenocarcinoma (HT-29), liver hepatocellular carcinoma (HepG-2), breast (MCF-7), colon carcinoma (HCT-8), and ovary (A2780) is reported. Remarkably, almost all complexes exhibit significant cytotoxic effects towards HepG-2, MCF-7, and HCT-8 cancer cell lines and complex 1 emerged as the most cytotoxic derivative in comparison with other complexes. The complexes 1-4 increase the production of reactive oxygen species (ROS) in MCF-7 cells. The new compounds also inhibit the enzyme thioredoxin reductase activity at nanomolar concentrations. Furthermore, the complexes induce major levels of cancer cell death by apoptosis that is in correlation with activity in cytotoxicity studies.
authors.affiliation: School of Chemistry, National University of Ireland, Galway, University Road, Galway, Ireland. LEILA.TABRIZI@nuigalway.ie and Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran. Chinif@cc.iut.ac.ir.
authors.forename: Leila
authors.identifier: http://orcid.org/0000-0002-3699-5869
authors.initials: L
authors.lastname: Tabrizi
authors.affiliation: Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran. Chinif@cc.iut.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Chiniforoshan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001554:Benzene / Q000737:chemistry*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007495:Iridium / Q000737:chemistry*; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D007495:Iridium; D004247:DNA; D001554:Benzene