Ru(II)/clotrimazole/diphenylphosphine/bipyridine complexes: Interaction with DNA, BSA and biological potential against tumor cell lines and Mycobacterium tuberculosis

J Inorg Biochem. 2016 Sep:162:135-145. doi: 10.1016/j.jinorgbio.2016.06.023. Epub 2016 Jun 25.

Abstract

Three ruthenium complexes [RuCl(CTZ)(bipy)(P-P)]PF6 [P-P=1,2-bis(diphenylphosphino)ethane (dppe-1), 1,4-bis(diphenylphosphino)butane (dppb-2) and 1,1'-bis(diphenylphosphino)ferrocene (dppf-3), bipy=2,2'-bipiridine and clotrimazole (CTZ) 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole] were synthesized. These complexes were characterized by a combination of elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, 1H, 13C{1H} and 31P{1H} nuclear magnetic resonance techniques, cyclic voltammetry and mass spectroscopy. Bovine serum albumin binding constants, which were in the range of 1.30-36.00×104M-1, and thermodynamic parameters suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. DNA interactions studied by spectroscopic titration, viscosity measurements, gel electrophoresis, circular dichroism, ethidium bromide displacement and reactions with guanosine and guanosine monophosphate indicated the DNA binding affinity primarily through non-covalent interactions. All complexes 1-3 were tested against the human carcinoma cell lines MCF-7 (breast), A549 (lung) and DU-145 (prostate) presenting promising IC50 values, between 0.50 and 14.00μM, in some cases lower than the IC50 for the reference drug (cisplatin). The antimicrobial activity assays of the complexes provided evidence that they are potential agents against mycobacterial infections, specifically against Mycobacterium tuberculosis H37Rv.

Keywords: Antitumor and anti-Mycobacterium tuberculosis; Clotrimazole; Ruthenium-bisdiphenylphosphine.

MeSH terms

  • 2,2'-Dipyridyl / chemistry*
  • A549 Cells
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / pharmacology
  • Cattle
  • Cell Line, Tumor
  • Clotrimazole / chemistry*
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / pharmacology
  • DNA / chemistry
  • Ethidium / chemistry
  • Ferrous Compounds / chemistry
  • Guanosine Monophosphate / chemistry
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Metallocenes
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / growth & development
  • Phosphines / chemistry
  • Ruthenium / chemistry*
  • Serum Albumin, Bovine / chemistry
  • Static Electricity
  • Structure-Activity Relationship
  • Thermodynamics
  • Viscosity

Substances

  • Antineoplastic Agents
  • Antitubercular Agents
  • Coordination Complexes
  • Ferrous Compounds
  • Metallocenes
  • Phosphines
  • Serum Albumin, Bovine
  • 2,2'-Dipyridyl
  • Ruthenium
  • Guanosine Monophosphate
  • DNA
  • calf thymus DNA
  • Ethidium
  • Clotrimazole
  • 1,1'-bis(diphenylphosphino)ferrocene