Ruthenium(II) phosphine/diimine/picolinate complexes: Inorganic compounds as agents against tuberculosis

Abstract: This paper describes the synthesis and characterization of four new ruthenium complexes containing 1,4 bis(diphenylphosphino)butane (dppb), 2-pyridinecarboxylic acid anion (pic) and the diimines [(2,2′-bipyridine (bipy), 4,4′-dimethyl-2,2′-bipyridine (Me-bipy), 4,4′-dichloro-2,2′-bipyridine (Cl-bipy) and 1,10-phenanthroline (phen) as ligands, with formulae [Ru(pic)(dppb)(bipy)]PF6 (SCAR01), [Ru(pic)(dppb)(Me-bipy)]PF6 (SCAR02), [Ru(pic)(dppb)(Cl-bipy)]PF6 (SCAR03) and [Ru(pic)(dppb)(phen)]PF6 (SCAR04). Additionally, the in vitro anti-Mycobacterium tuberculosis (MTB) activity, cytotoxicity and activity against in vitro infection of these complexes and two more complexes, cis-[Ru(pic)(dppe)2]PF6 (SCAR05) and cis-[RuCl2(dppb)(bipy)] (SCAR06), and their free ligands are described and discussed. All compounds showed excellent MIC against MTB, low cytotoxicity and a selectivity index higher than 10. Also, all compounds showed significant intracellular inhibition and the compound SCAR05 showed a better activity than rifampin and SQ109. This is the first report of activity against in vitro infection of ruthenium compounds. [Copyright &y& Elsevier]