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

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• 作者：Fernando R. Pavan^a ; ^{pavanfer@yahoo.com.br} ; Gustavo V. Poelhsitz^b ; Marilia I.F. Barbosa^c ; Sergio R.A. Leite^d ; Alzir A. Batista^c ; ^{daab@power.ufscar.br} ; Javier Ellena^e ; Leticia S. Sato^a ; Scott G. Franzblau^f ; Virtudes Moreno^g ; Dinorah Gambino^h ; Clarice Q.F. Leite^a ; ^{leitecqf@fcfar.unesp.br}
• 关键词：Mycobacterium tuberculosis ; Drug resistance ; Ruthenium ; Phosphine/diimine/picolinate
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October, 2011
• 年：2011
• 卷：46
• 期：10
• 页码：5099-5107
• 全文大小：674 K

文摘

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¡ä-bipyridine (bipy), 4,4¡ä-dimethyl-2,2¡ä-bipyridine (Me-bipy), 4,4¡ä-dichloro-2,2¡ä-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.