Heteroleptic complexes of antifungal drugs with the silver ion

GIULIDORI, CECILIA; MOSCONI, NATALIA; TOPLIKAR, BRENDA ; VEGA, MARISA; WILLIAMS, PATRICIA; SVETAZ, LAURA; RAIMONDI, MARCELA; RIZZOTTO, MARCELA

Villa Carlos Paz

Congreso; 13a Conferencia Latinoamericana de Físico-Química Orgánica; 2015

In spite of a large number of antibiotics and chemotherapeutics available for medical use, at the same time the emergence of old and new antibiotic resistance created in the last decades revealed a substantial medical need for new classes of antimicrobial agents.Many heterocyclic compounds containing benzimidazoles, which are the nucleolus of albendazole are a subject of interest to medicinal chemistry because of the broad spectrum of their biological and pharmaceutical properties. Investigation of the biological activity of complex compounds is a field that has developed over the years, because the antimicrobial activity of active drugs is often enhanced by complexation with metal ions. Here we report the obtaining, characterization by elemental analysis, FTIR (4,000 to 400 cm-1, using the KBr pellet technique) and NMR (1H NMR, 300.1 MHz; 13C NMR, 50.3 MHz) spectroscopies and antifungal properties of two heteroleptic complexes of albz with Ag (I), using KSCN and o-phenanthroline (phen) as the second ligand respectively. Obtaining of the complexes: by mixing of albz (dissolved in glacial HAc), with the second ligand and AgNO3 (aq) in a 1:1:1 mole ratio. Elemental analysis of the obtained powders gave satisfactory results for [Ag(albz)(SCN)], AgC13H15N4O2S2, white solid, calculated MM 431 g mol-1 and [Ag(albz)(phen)2]NO3?H2O, AgC36H33N8O6S, pale yellow solid, calculated MM: 813 g mol-1 . 1H NMR spectra show that albendazole retains its two acidic protons in both complexes. Infrared spectrum suggests a coordination of the silver ion with the C=O and the Nbenzimidazole of albz and with the N of the thiocyanate ion for the [Ag(albz)SCN] complex, while the IR spectrum of the albz-phen silver complex shows the presence of both ligands and nitrate. These results are in agreement with the NMR ones. Minimal Inhibitory Concentration (MIC) and minimal fungicidal concentration (MFC) of Ag-Habz and AgNO3 were determined by using broth microdilution techniques according with the Clinical and Laboratory Standards Institute. Both MIC and MFC were confirmed by two replicates. Tested fungi: Ca: Candida albicans ATCC 10231; Ct: Candida tropicalis C 131; Cn: Cryptococcus neoformans ATCC 32264; Afl: Aspergillus flavus ATCC 9170; Afu: Aspergillus fumigatus ATCC 26934; Ani: Aspergillus niger ATCC 9029; Mg: Microsporum gypseum C 115; Tr: Trichophyton rubrum C 113; Tm: Trichophyton mentagrophytes ATCC 9972. Both complexes showed a moderate antifungal activity with all the assayed fungi,mainly with Ca and Ct, with which albz was not active.