Biological activity of two novel zinc(II) complexes with NSAID mefenamic acid

Abstract

Zinc(II) mefenamate [Zn(mef)2] (1) along with two novel Zn(II) crystalline complexes with Hmef (mefenamic acid) [Zn(dmso)2(mef)2] (2) and [Zn(cyclam)(mef)2] (3) were synthesized and characterized by infrared spectroscopy, elemental and thermal analysis. Crystal structures of complexes 2 and 3 were determined by single-crystal X-ray structure analysis. The biological activity of complexes was investigated using various methods. First, the ability of the complexes to scavenge radicals [2,2-diphenyl-1-picrylhydrazyl—DPPH and diammonium 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonate)—ABTS] was investigated, indicating selective scavenging activity of studied compounds for ABTS·+ in comparison to DPPH·. The complexes 2 and 3 are more active than the free Hmef. Second, the interaction of the complexes with serum albumins was investigated and obtained binding constants are within optimal range for transport in bloodstream. Third, the interaction of complexes with fish sperm DNA (FS-DNA) was studied by UV–Vis titration and competitive binding studies with ethidium bromide (EB). The obtained values of binding constants calculated from UV–Vis measurements and fluorescence measurements, respectively, indicates the strongest binding for complex 3. Fourth, antimicrobial activity of compounds 1–3 was studied against bacteria (S. aureus and E. coli), yeast (C. parapsilosis) and filamentous fungi (R. oryzae, A. alternata, M. gypseum); complex 1 indicates highest activity against filamentous fungi R. oryzae and A. alternate whereas complex 2 displays highest antimicrobial activity against both Gram-positive and Gram-negative bacteria and yeast.