Bis‐picolinamide Ruthenium(III) Dihalide Complexes: Dichloride‐to‐Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity. Issue 26 (7th April 2017)

• Record Type: Journal Article
• Authors: Basri, Aida M.; Lord, Rianne M.; Allison, Simon J.; Rodríguez‐Bárzano, Andrea; Lucas, Stephanie J.; Janeway, Felix D.; Shepherd, Helena J.; Pask, Christopher M.; Phillips, Roger M.; McGowan, Patrick C.
• Is Part Of: Chemistry. Volume 23:Issue 26(2017)
• Page Start: 6341
• Page End: 6356
• Publication Date: 2017-04-07
• Subjects: antitumor agents -- cytotoxicity -- isomers -- ligand effects -- ruthenium; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201605960
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A library of new bis‐picolinamide ruthenium(III) dihalide complexes of the type [RuX2 L2 ] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N, N) and the other bound (N, O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2 L2 ] complexes but upon a halide exchange reaction to yield [RuI2 L2 ], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2 L2 ] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2 L2 ] complexes displayed potent activity against the A2780cis (cisplatin‐resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non‐cancer ARPE‐19 cells was also tested. The [RuI2 L2 ] complexes were found to be more potent than the [RuCl2 L2 ] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold. Abstract : Tricks of the trade : This report presents compounds of the type [RuX2 L2 ] (X=Cl or I, L=a functionalised picolinamide ligand; see figure). The [RuCl2 L2 ] complexes exhibit a mixture of isomers and are active against a range of cancer cell lines. Upon a halide exchange reaction to their [RuI2 L2 ] analogues, a single stable trans ‐iodide isomer is observed. These compounds show high cytotoxicity in the nanomolar range, are cytotoxic under hypoxic conditions and selective towards cancerous cells.