title: Structure-activity relationships for cytotoxic ruthenium(II) arene complexes containing N,N-, N,O-, and O,O-chelating ligands.
abstract: We report structure-activity relationships for organometallic RuII complexes of the type [(eta6-arene)Ru(XY)Cl]Z, where XY is an N,N- (diamine), N,O- (e.g., amino acidate), or O,O- (e.g., beta-diketonate) chelating ligand, the arene ranges from benzene derivatives to fused polycyclic hydrocarbons, and Z is usually PF6. The X-ray structures of 13 complexes are reported. All have the characteristic "piano-stool" geometry. The complexes most active toward A2780 human ovarian cancer cells contained XY=ethylenediamine (en) and extended polycyclic arenes. Complexes with polar substituents on the arene or XY=bipyridyl derivatives exhibited reduced activity. The activity of the O,O-chelated complexes depended strongly on the substituents and on the arene. For arene=p-cymene, XY=amino acidate complexes were inactive. Complexes were not cross-resistant with cisplatin, and cross-resistance to Adriamycin was circumvented by replacing XY=en with 1,2-phenylenediamine. Some complexes were also active against colon, pancreatic, and lung cancer cells.
authors.affiliation: School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK, and University of Edinburgh Centre for Cancer Research, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Abraha
authors.initials: A
authors.lastname: Habtemariam
authors.forename: Michael
authors.initials: M
authors.lastname: Melchart
authors.forename: Rafael
authors.initials: R
authors.lastname: Fernandez
authors.forename: Simon
authors.initials: S
authors.lastname: Parsons
authors.forename: Iain D H
authors.initials: ID
authors.lastname: Oswald
authors.forename: Andrew
authors.initials: A
authors.lastname: Parkin
authors.forename: Francesca P A
authors.initials: FP
authors.lastname: Fabbiani
authors.forename: James E
authors.initials: JE
authors.lastname: Davidson
authors.forename: Alice
authors.initials: A
authors.lastname: Dawson
authors.forename: Rhona E
authors.initials: RE
authors.lastname: Aird
authors.forename: Duncan I
authors.initials: DI
authors.lastname: Jodrell
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D002945:Cisplatin / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003959:Diamines / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000737:chemistry; D012428:Ruthenium; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D002614:Chelating Agents; D003959:Diamines; D008024:Ligands; D009942:Organometallic Compounds; D011083:Polycyclic Compounds; D015082:2,2'-Dipyridyl; D012428:Ruthenium; D004317:Doxorubicin; D016190:Carboplatin; D002945:Cisplatin