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

Author(s):Show less -

Pavan, Fernando R. ^[1] ; Poelhsitz, Gustavo V. ^[2] ; Barbosa, Marilia I. F. ^[3] ; Leite, Sergio R. A. ^[4] ; Batista, Alzir A. ^[3] ; Ellena, Javier ^[5] ; Sato, Leticia S. ^[1] ; Franzblau, Scott G. ^[6] ; Moreno, Virtudes ^[7] ; Gambino, Dinorah ^[8] ; Leite, Clarice Q. F. ^[1]

Affiliation

^[1] Univ Estadual Paulista, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Quim, BR-38400902 Uberlandia, MG - Brazil

^[3] Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[4] Univ Estadual Paulista, Inst Quim, BR-14800900 Araraquara, SP - Brazil

^[5] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

^[6] Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL - USA

^[7] Univ Barcelona, Dept Quim Inorgan, E-08028 Barcelona - Spain

^[8] Univ Republica, Fac Quim, Catedra Quim Inorgan, Dept Estrella Campos, Montevideo 11800 - Uruguay

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 46, n. 10, p. 5099-5107, OCT 2011.
• Web of Science Citations: 53

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)]PF(6) (SCAR01), {[}Ru(pic)(dppb) (Me-bipy)]PF(6) (SCAR02), {[}Ru(Pic)(dPPb)(Cl-bipy]PF(6) (SCAR03) and {[}Ru(pic)(dppb)(phen)]PF(6) (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)]PF(6)(SCAR05) and cis-{[}RuCl(2)(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. (C) 2011 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 08/10390-2 - Determination of pre-clinical profile in vitro and in vivo anti-tuberculosis activity of ruthenium(II)phosphine / picolinate complexes
• Grantee: Fernando Rogério Pavan
• Support Opportunities: Scholarships in Brazil - Doctorate