A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity

7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(eta(6)-p-cymene)(CipA(-H))Cl], (2) have been synthesised and the x-ray crystal structures of 1.1.3H(2)O center dot 0.6CH(3)OH and 2.CH3OH center dot 0.5H(2)O determined. The complex adopts a typical pseudo octahedral 'piano-stool' geometry, with Ru(II) pi-bonded to the p-cymene ring and sigma-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low mu M 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 mu M 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 beta-lactam antibiotics. (C) 2016 The Authors. Published by Elsevier Inc.