Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, CEP 14801-902, Araraquara, SP, Brazil.
Eur J Med Chem. 2011 Oct;46(10):5099-107. doi: 10.1016/j.ejmech.2011.08.023. Epub 2011 Aug 23.
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.
本文描述了四种新的钌配合物的合成与表征，这些配合物含有 1,4-双（二苯基膦）丁烷（dppb）、2-吡啶甲酸阴离子（pic）和二亚胺[(2,2'-联吡啶（bipy）、4,4'-二甲基-2,2'-联吡啶（Me-bipy）、4,4'-二氯-2,2'-联吡啶（Cl-bipy）和 1,10-菲咯啉（phen）作为配体，其化学式为[Ru(pic)(dppb)(bipy)]PF(6)（SCAR01）、[Ru(pic)(dppb)(Me-bipy)]PF(6)（SCAR02）、[Ru(pic)(dppb)(Cl-bipy)]PF(6)（SCAR03）和[Ru(pic)(dppb)(phen)]PF(6)（SCAR04）。此外，还描述和讨论了这些配合物以及另外两种配合物 cis-[Ru(pic)(dppe)(2)]PF(6)（SCAR05）和 cis-[RuCl(2)(dppb)(bipy)]（SCAR06）及其游离配体的体外抗结核分枝杆菌（MTB）活性、细胞毒性和体外感染活性。所有化合物对 MTB 的 MIC 均表现出优异的抑制活性，细胞毒性低，选择性指数高于 10。此外，所有化合物均表现出显著的细胞内抑制作用，化合物 SCAR05 的活性优于利福平（rifampin）和 SQ109。这是首例关于钌化合物对体外感染活性的报道。
