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>