10779/rcsi.10991483.v1 Ziga Ude Ziga Ude Isolda Romero-Canelón Isolda Romero-Canelón Brendan Twamley Brendan Twamley Deirdre Fitzgerald-Hughes Deirdre Fitzgerald-Hughes Peter J. Sadler Peter J. Sadler Celine Marmion Celine Marmion A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity. Royal College of Surgeons in Ireland 2019 Anti-Cancer Anti-Microbial Ciprofloxacin Crystal Structure Ruthenium(II) Ruthenium(II)–Arene 2019-11-23 11:50:43 Journal contribution https://repository.rcsi.com/articles/journal_contribution/A_novel_dual-functioning_ruthenium_II_-arene_complex_of_an_anti-microbial_ciprofloxacin_derivative_-_Anti-proliferative_and_anti-microbial_activity_/10991483 <p>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.</p>