Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Synthesis and in vitro antifungal activity of isoniazid-derived hydrazones against Coccidioides posadasii

2016; Elsevier BV; Volume: 98; Linguagem: Inglês

10.1016/j.micpath.2016.06.022

1096-1208

Rossana de Aguiar Cordeiro, Charlline Vládia Silva de Melo, Francisca Jakelyne de Farias Marques, Rosana Serpa, Antônio José de Jesus Evangelista, Érica Pacheco Caetano, Jair Mafezoli, Maria da Conceição Ferreira de Oliveira, Marcos Reinaldo da Silva, Tereza de Jesus Pinheiro Gomes Bandeira, José Luciano Bezerra Moreira, Raimunda Sâmia Nogueira Brilhante, Marcos Fábio Gadelha Rocha, José Júlio Costa Sidrim,

Nail Diseases and Treatments

Coccidioidomycosis is a potentially severe infection caused by dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Although guidelines are well established, refractory disease is a matter of concern in the clinical management of coccidioidomycosis. In the present study three isoniazid-derived hydrazones N'-[(E)-1-(4-methoxyphenyl)ethylidene]pyridine-4-carbohydrazide, N'-[(E)-1-(4-methylphenyl)ethylidene]pyridine-4-carbohydrazide, and N'-[(E)-1-(phenyl)ethylidene]pyridine-4-carbohydrazide were synthesized and evaluated for antifungal activity against C. posadasii. Susceptibility assays were performed by macrodilution testing. Interactions between the hydrazones and amphotericin B or itraconazole were evaluated by the checkerboard method. We also investigated the impairment of such compounds on cell ergosterol and membrane integrity. The synthesized molecules were able to inhibit C. posadasii in vitro with MIC values that ranged from 25 to 400 μg/mL. Drug interactions between synthesized molecules and amphotericin B proved synergistic for the majority of tested isolates; regarding itraconazole, synergism was observed only when strains were tested against N'-[(E)-1-(phenyl)ethylidene]pyridine-4-carbohydrazide. Reduction of cellular ergosterol was observed when strains were challenged with the hydrazones alone or combined with antifungals. Only N'-[(E)-1-(4-methylphenyl)ethylidene]pyridine-4-carbohydrazide altered membrane permeability of C. posadasii cells. Isoniazid-derived hydrazones were able to inhibit C. posadasii cells causing reduction of ergosterol content and alterations in the permeability of cell membrane. This study confirms the antifungal potential of hydrazones against pathogenic fungi.