Synthesis, characterization, lipophilicity and antifungal properties of three new complexes of sulfamerazine (HSMR) with Ag(I): [Ag(SMR)], [Ag2(SMR)SCN] and [Ag(SMR)o-phenanthroline

Abstract

Fungal infections, whose treatment is complicated by the appearance of the resistance to antifungal drugs, remain a major problem. Consequently, there is a critical need for new antifungal agents. Complexation of the silver(I) cation with different ligands reduces adverse effects and increases its therapeutic potential and has led to a large number of promising antibacterial, antifungal and anticancer compounds. The interest in metal–sulfanilamide derivatives has been stimulated by the successful introduction of a silver-sulfadiazine complex, still in current use. Sulfamerazine (HSMR) is a long-acting sulfanilamide antibacterial agent, which can be used to treat bronchitis, prostatitis and urinary tract infections. As a continuation of our work on metal complexes of sulfa drugs, in this paper we report the synthesis, characterization by elemental analysis, thermogravimetric analyses (TG), proton nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectra (FTIR) besides principal component analysis (PCA) spectroscopies, lipophilicity and antifungal properties of three new complexes of silver(I) with HSMR, one homoleptic: [Ag(SMR)], and two heteroleptic, using as second ligand KSCN: [Ag2(SMR)SCN] and o-phenanthroline (phen): [Ag(SMR)phen], named as (1), (2) and (3) respectively. 1H NMR spectra show that the sulfonamide moiety loses its acidic proton in all complexes, in agreement with the FTIR results. Lipophilicity: log Koctanol/water values were similarly to other sulfa-metal complexes, indicating low affinity for animal fat tissues. The three complexes showed a moderate antifungal activity, especially (3) mainly against Candida albicans, Cryptococcus neoformans and the dermatophytes Microsporum gypseum, Trichophyton rubrum and T. mentagrophytes. None of the tested fungi was inhibited by the free ligand, NaSMR. Considering these results, the studied complexes could be good candidates for further pharmaceutical studies.