title: Synthesis and evaluation of new polynuclear organometallic Ru(II), Rh(III) and Ir(III) pyridyl ester complexes as in vitro antiparasitic and antitumor agents.
abstract: New polynuclear organometallic Platinum Group Metal (PGM) complexes containing di- and tripyridyl ester ligands have been synthesised and characterised using analytical and spectroscopic techniques including (1)H, (13)C NMR and infrared spectroscopy. Reaction of these polypyridyl ester ligands with either [Ru(p-cymene)Cl2]2, [Rh(C5Me5)Cl2]2 or [Ir(C5Me5)Cl2]2 dimers yielded the corresponding di- or trinuclear organometallic complexes. The polyaromatic ester ligands act as monodentate donors to each metal centre and this coordination mode was confirmed upon elucidation of the molecular structures for two of the dinuclear complexes. The di- and trinuclear PGM complexes synthesized were evaluated for inhibitory effects on the human protozoal parasites Plasmodium falciparum strain NF54 (chloroquine sensitive), Trichomonas vaginalis strain G3 and the human ovarian cancer cell lines, A2780 (cisplatin-sensitive) and A2780cisR (cisplatin-resistant) cell lines. All of the complexes were observed to have moderate to high antiplasmodial activities and the compounds with the best activities were evaluated for their ability to inhibit formation of synthetic hemozoin in a cell free medium. The in vitro antitumor evaluation of these complexes revealed that the trinuclear pyridyl ester complexes demonstrated moderate activities against the two tumor cell lines and were also less toxic to model non-tumorous cells.
authors.affiliation: Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa. gregory.smith@uct.ac.za.
authors.forename: Prinessa
authors.initials: P
authors.lastname: Chellan
authors.forename: Kirkwood M
authors.initials: KM
authors.lastname: Land
authors.forename: Ajit
authors.initials: A
authors.lastname: Shokar
authors.forename: Aaron
authors.initials: A
authors.lastname: Au
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: An
authors.forename: Dale
authors.initials: D
authors.lastname: Taylor
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Tina
authors.initials: T
authors.lastname: Riedel
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Smith
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007495:Iridium / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry; D012995:Solubility; D014246:Trichomonas vaginalis / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000977:Antiparasitic Agents; D009942:Organometallic Compounds; D011725:Pyridines; D007495:Iridium; D012428:Ruthenium; D012238:Rhodium; C023666:pyridine