da Silva Juliana P, Silva Isabel C, Pavan Fernando R, Back Davi F, de Araujo Márcio P
Departamento de Química, Universidade Federal do Paraná, Centro Politécnico, CP 19081, CEP 81531-980 Curitiba, PR, Brazil.
Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Univ. Estadual Paulista, CEP: 14800-900 Araraquara, SP, Brazil.
J Inorg Biochem. 2017 Aug;173:134-140. doi: 10.1016/j.jinorgbio.2017.04.008. Epub 2017 Apr 9.
Several ruthenium complexes have been investigated regarding anti-Mycobacterium tuberculosis (anti-MTb) activity, with some diphosphine-containing ruthenium complexes comparable to first and second line drugs. However, to the best of our knowledge, there is no PNP-containing ruthenium complexes applied as metallodrugs. Thus, this study focused on the synthesis, characterization and anti-MTb activity of a new series of coordination compounds with general formula [RuCl(η-p-cymene)(PNP)]X (R=CHPy (Py=pyridine)-[1a], CHPh (Ph=phenyl)-[1b], Ph-[1c] and p-tol (p-tol=p-tolyl)-[1d]; X=PF or BF). The complexes were fully characterized by NMR (H, P{H}), vibrational spectroscopy (FTIR), ESI-MS, molar conductance, elemental analysis and X-ray diffraction studies. The molecular structures of [1a]PF, [1c]BF and [1d]PF were determined and confirm the spectroscopic and ESI-MS data. The complexes were used in anti-MTb trials, and the preliminary results are presented. The complexes are promising anti-MTb agents with MIC (Minimum Inhibitory Concentration of compounds required to inhibit the growth of 90% of MTb) values comparable with the Ethambutol, the reference drug used in this work, and complex [1a]BF presented the highest selectivity index.
人们已经对几种钌配合物的抗结核分枝杆菌(抗MTb)活性进行了研究,一些含二膦的钌配合物的活性与一线和二线药物相当。然而,据我们所知,尚无含PNP的钌配合物用作金属药物。因此,本研究重点关注了一系列通式为[RuCl(η-p-异丙基苯)(PNP)]X(R = CHPy(Py = 吡啶)-[1a]、CHPh(Ph = 苯基)-[1b]、Ph-[1c]和p-tol(p-tol = 对甲苯基)-[1d];X = PF 或 BF)的新型配位化合物的合成、表征及抗MTb活性。通过核磁共振(H、P{H})、振动光谱(FTIR)、电喷雾电离质谱(ESI-MS)、摩尔电导率、元素分析和X射线衍射研究对这些配合物进行了全面表征。确定了[1a]PF₂、[1c]BF₄和[1d]PF₆的分子结构,证实了光谱和ESI-MS数据。将这些配合物用于抗MTb试验,并给出了初步结果。这些配合物是很有前景的抗MTb药物,其最低抑菌浓度(MIC,抑制90%的MTb生长所需化合物的最低浓度)值与本研究中使用的参比药物乙胺丁醇相当,并且配合物[1a]BF₄具有最高的选择性指数。