Silver(i) complexes with 2-acetylpyridinebenzoylhydrazones exhibit antimicrobial effects against yeast and filamentous fungi

Abstract

Complexes [Ag(H2AcPh)NO₃] (1) [Ag(H2AcpCH₃Ph)NO₃] (2) [Ag(H2AcpClPh)NO₃] (3) and [Ag(H2AcpNO₂Ph)NO₃] (4) were obtained with 2-acetylpyridinebenzoylhydrazone (H2AcPh) and its para-methyl-(H2AcpCH₃Ph), para-chloro-(H2AcpClPh) and para-nitro-benzoylhydrazone (H2AcpNO₂Ph) derivatives. In general, upon coordination to silver(I) the antimicrobial activity of the hydrazones increased against yeast and filamentous fungi. Several compounds proved to be as or more active than nystatin against the filamentous fungi. SAR studies showed that, in most of the cases, the antifungal activities against the Candida strains correlate well with the energy of the HOMO orbital, suggesting that an external electrophilic attack to these compounds or an electron donation from these compounds to the targets might be involved in their biochemical pathways. On the other hand, for the Aspergillus and Penicillium strains the antifungal activities of the compounds under study correlate well with log P. Hence, their ability to transpose biological membranes might be responsible for their capacity to reach the target. Taking into consideration the reported resistance to the current antifungal drugs and their adverse side effects, the compounds under study deserve to be further investigated as antimicrobial drug candidates.