title: A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity.
abstract: 7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics.
authors.affiliation: Centre for Synthesis and Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Ziga
authors.initials: Z
authors.lastname: Ude
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Isolda
authors.initials: I
authors.lastname: Romero-Canelón
authors.affiliation: School of Chemistry, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Twamley
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Fitzgerald Hughes
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK. Electronic address: P.J.Sadler@warwick.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
authors.affiliation: Centre for Synthesis and Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland. Electronic address: cmarmion@rcsi.ie.
authors.forename: Celine J
authors.initials: CJ
authors.lastname: Marmion
mesh_terms: D000072283:A549 Cells; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D002939:Ciprofloxacin / Q000737:chemistry*; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D000081007:Cymenes; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D045325:HCT116 Cells; D006801:Humans; D039821:Monoterpenes / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002413:Cations, Divalent; D056831:Coordination Complexes; D000081007:Cymenes; D039821:Monoterpenes; D009942:Organometallic Compounds; D016159:Tumor Suppressor Protein p53; C007210:4-cymene; D002939:Ciprofloxacin; D012428:Ruthenium; D002945:Cisplatin
keywords: Anti-cancer; Anti-microbial; Ciprofloxacin; Crystal structure; Ruthenium(II); Ruthenium(II)–arene