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.
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
Ying
Y
Fu
Abraha
A
Habtemariam
Ana M
AM
Pizarro
Sabine H
SH
van Rijt
David J
DJ
Healey
Patricia A
PA
Cooper
Steven D
SD
Shnyder
Guy J
GJ
Clarkson
Peter J
PJ
Sadler
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