Organometallic osmium arene complexes with potent cancer cell cytotoxicity.
Iodido osmium(II) complexes [Os(η(6)-arene)(XY)I](+) (XY = p-hydroxy or p-dimethylaminophenylazopyridine, arene = p-cymene or biphenyl) are potently cytotoxic at nanomolar concentrations toward a panel of human cancer cell lines; e.g., IC(50) = 140 nM for [Os(η(6)-bip)(azpy-NMe(2))I](+) toward A2780 ovarian cancer cells. They exhibit low toxicity and negligible deleterious effects in a colon cancer xenograft model, giving rise to the possibility of a broad therapeutic window. The most active complexes are stable and inert toward aquation. Their cytotoxic activity appears to involve redox mechanisms.
Fu
Ying
Y
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
Habtemariam
Abraha
A
Pizarro
Ana M
AM
van Rijt
Sabine H
SH
Healey
David J
DJ
Cooper
Patricia A
PA
Shnyder
Steven D
SD
Clarkson
Guy J
GJ
Sadler
Peter J
PJ
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D000081007:Cymenes; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D015394:Molecular Structure; D039821:Monoterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009992:Osmium; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001391:Azo Compounds; D001713:Biphenyl Compounds; D056831:Coordination Complexes; D000081007:Cymenes; D016166:Free Radical Scavengers; D039821:Monoterpenes; D011725:Pyridines; D017382:Reactive Oxygen Species; C007210:4-cymene; D009992:Osmium; D005978:Glutathione; D000111:Acetylcysteine