title: Mirror-image organometallic osmium arene iminopyridine halido complexes exhibit similar potent anticancer activity.
abstract: Four chiral Os(II) arene anticancer complexes have been isolated by fractional crystallization. The two iodido complexes, (S(Os),S(C))-[Os(η(6)-p-cym)(ImpyMe)I]PF6 (complex 2, (S)-ImpyMe: N-(2-pyridylmethylene)-(S)-1-phenylethylamine) and (R(Os),R(C))-[Os(η(6)-p-cym)(ImpyMe)I]PF6 (complex 4, (R)-ImpyMe: N-(2-pyridylmethylene)-(R)-1-phenylethylamine), showed higher anticancer activity (lower IC50 values) towards A2780 human ovarian cancer cells than cisplatin and were more active than the two chlorido derivatives, (S(Os),S(C))-[Os(η(6)-p-cym)(ImpyMe)Cl]PF6, 1, and (R(Os),R(C))-[Os(η(6)-p-cym)(ImpyMe)Cl]PF6, 3. The two iodido complexes were evaluated in the National Cancer Institute 60-cell-line screen, by using the COMPARE algorithm. This showed that the two potent iodido complexes, 2 (NSC: D-758116/1) and 4 (NSC: D-758118/1), share surprisingly similar cancer cell selectivity patterns with the anti-microtubule drug, vinblastine sulfate. However, no direct effect on tubulin polymerization was found for 2 and 4, an observation that appears to indicate a novel mechanism of action. In addition, complexes 2 and 4 demonstrated potential as transfer-hydrogenation catalysts for imine reduction.
authors.affiliation: Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL (UK), Fax: (+44) 024-76523819.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.forename: Rina
authors.initials: R
authors.lastname: Soni
authors.forename: María J
authors.initials: MJ
authors.lastname: Romero
authors.forename: Ana M
authors.initials: AM
authors.lastname: Pizarro
authors.forename: Luca
authors.initials: L
authors.lastname: Salassa
authors.forename: Guy J
authors.initials: GJ
authors.lastname: Clarkson
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Hearn
authors.forename: Abraha
authors.initials: A
authors.lastname: Habtemariam
authors.forename: Martin
authors.initials: M
authors.lastname: Wills
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry*; D009992:Osmium / Q000737:chemistry / Q000627:therapeutic use*; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D009992:Osmium
keywords: anticancer agents; arene ligands; chirality; organometallic; osmium