Bis(diphenylphosphino)amines-containing ruthenium cymene complexes as potential anti-Mycobacterium tuberculosis agents

J Inorg Biochem. 2017 Aug:173:134-140. doi: 10.1016/j.jinorgbio.2017.04.008. Epub 2017 Apr 9.

Abstract

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(η6-p-cymene)(PNRP)]X (R=CH2Py (Py=pyridine)-[1a], CH2Ph (Ph=phenyl)-[1b], Ph-[1c] and p-tol (p-tol=p-tolyl)-[1d]; X=PF6- or BF4-). The complexes were fully characterized by NMR (1H, 31P{1H}), vibrational spectroscopy (FTIR), ESI-MS, molar conductance, elemental analysis and X-ray diffraction studies. The molecular structures of [1a]PF6, [1c]BF4 and [1d]PF6 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 MIC90 (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]BF4 presented the highest selectivity index.

MeSH terms

  • Aniline Compounds / chemistry*
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Crystallography, X-Ray
  • Cymenes
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Monoterpenes / chemistry*
  • Mycobacterium tuberculosis / drug effects*
  • Phosphines / chemistry*
  • Ruthenium Compounds / chemistry*
  • Ruthenium Compounds / pharmacology*
  • X-Ray Diffraction

Substances

  • Aniline Compounds
  • Anti-Bacterial Agents
  • Cymenes
  • Monoterpenes
  • Phosphines
  • Ruthenium Compounds
  • bis(diphenylphosphino)amine
  • 4-cymene