Heteroleptic complexes of antifungal drugs with the silver ion

C. GUILDORI; N. MOSCONI; B. TOPLIKAR; M. VEGA; L SVETAZ; P.A:M. WILLIAMS; M. RAIMONDI; M. RIZZOTTO

Conferencia; 13th Latin American Conference on Physical Organic Chemistry; 2015

Heterolepticcomplexes of antifungal drugs with the silver ion Cecilia Giulidori1,Natalia Mosconi1, Brenda Toplikar1, Marisa Vega1,Patricia Williams2, Laura Svetaz1, Marcela Raimondi1,Marcela Rizzotto1  1IQUIR, Facultyof Biochemistry and Pharmacy, UNR, Suipacha 531 Rosario Argentina, 2CEQUINOR,Facultad de Ciencias Exactas, UNLP, cc. 962 La Plata, Argentina  In spite ofa large number of antibiotics and chemotherapeutics available for medical use,at the same time the emergence of old and new antibiotic resistance created inthe last decades revealed a substantial medical need for new classes ofantimicrobial agents.Many heterocyclic compoundscontaining benzimidazoles, which are the nucleolus of albendazole (albz, Fig.1) are a subject of interest to medicinal chemistry because of the broadspectrum of their biological and pharmaceutical properties. Investigationof the biological activity of complex compounds is a field that has developedover the years, because the antimicrobial activity ofactive drugs is often enhanced by complexation with metal ions. Here wereport 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 propertiesof two  heteroleptic complexes of albzwith Ag (I), using KSCN and o-phenanthroline (phen)  as the second ligand respectively. Obtainingof the complexes: by mixing of albz (dissolved in glacial HAc), with the secondligand and AgNO3 (aq) in a 1:1:1 mole ratio. Elemental analysis ofthe obtained powders gave satisfactory results for [Ag(albz)(SCN)], AgC13H15N4O2S2,white solid, calculated MM 431  g mol-1and [Ag(albz)(phen)2]NO3·H2O, AgC36H33N8O6S,pale yellow solid, calculated MM: 813 g mol-1 . 1HNMR spectra show that albendazole retains its two acidic protons in bothcomplexes. Infrared spectrum suggests a coordination of the silver ion with theC=O and the Nbenzimidazole of albzand with the N of the thiocyanate ion (Fig. 2) for the [Ag(albz)SCN]complex, whilethe IR spectrum of the albz-phen silver complex shows the presence of bothligands and nitrate (Fig. 3). These results are in agreement with the NMR ones.Minimal Inhibitory Concentration (MIC) and  minimal fungicidal concentration (MFC) ofAg-Habz and AgNO3  weredetermined by using broth microdilution techniques according with the Clinicaland Laboratory Standards Institute.  BothMIC 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. Bothcomplexes showed a moderate antifungal activity with all the assayed fungi,mainlywith Ca and Ct, with which  albz was notactive.