Synthesis and Structure Elucidation of New NSAID Diphosphine Ruthenium(II) Complexes as Potential Anticancer Agents:...

New diphosphine ruthenium-(II) complexes with nonsteroidal anti-inflammatory drugs (NSAID) derivatives with general formula [Ru-(L)-(dppe)₂]-PF₆ [dppe = 1,2-bis(diphenylphosphine)-ethane and (L) corresponds to fenamate (fe^-) (Complex 1), mefenamate (me^-) (Complex 2), tolfenamate (tol^-) (Complex 3) or flufenamate (flu^-) (Complex 4)] were synthesized. All compounds were characterized by several techniques, including ¹H, ¹³C-{¹H} and ³¹P-{¹H} NMR, cyclic voltammetry, conductivity, elemental analysis, ultraviolet/visible absorption spectroscopy, infrared absorption spectroscopy and single crystal X-ray diffraction. ct-DNA (Calf-Thymus DNA) interaction studies by spectroscopic titrations and viscosity measurements demonstrated that the complexes may interact weakly with ct-DNA, considering that the complexes are cationic and that DNA carries a negative charge due to its phosphate groups, electrostatic interactions could occur. The complexes showed a moderate interaction with Bovine Serum Albumin (BSA) mediated by both dynamic and static quenching mechanisms. Also, the cytotoxic activity of the complexes was evaluated against breast (MDA-MB-231) and lung (A549) tumor cell lines and nontumor lung (MRC-5) cell lines. All complexes showed cytotoxicity against the cell lines investigated, with IC₅₀ values in the range of 0.94-17.71 μM. [Ru-(me)-(dppe)₂]-PF₆ showed a high selectivity index against the A549 cell line. For MDA-MB-231 cell line, the most selective complex was [Ru-(fe)-(dppe)₂]-PF₆. Except for [Ru-(tol)-(dppe)₂]-PF₆, all other complexes were more cytotoxic than cisplatin, making them promising compounds.