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Title in Portuguese: Synthesis and antifungal activity In vitro of isoniazid derivatives against histoplasma capsulatum var. capsulatum
Author: Cordeiro, Rossana de Aguiar
Marques, Francisca Jakelyne de Farias
Cordeiro, Rebecca de Aguiar
Silva, Marcos Reinaldo da
Malaquias, Angela Donato Maia
Melo, Charlline Vládia Silva de
Mafezoli, Jair
Oliveira, Maria da Conceição Ferreira de
Brilhante, Raimunda Sâmia Nogueira
Rocha, Marcos Fábio Gadelha
Bandeira, Tereza de Jesus Pinheiro Gomes
Sidrim, José Júlio Costa
Keywords: Histoplasma
Anfotericina B
Issue Date: May-2014
Publisher: Antimicrobial Agents and Chemotherapy
Citation: CORDEIRO, R. A. et al. Synthesis and antifungal activity in vitro of isoniazid derivatives against histoplasma capsulatum var. capsulatum. Antimicrobial Agents and Chemotherapy, Bethesda, v. 58, n. 5, p. 2504-2511, maio, 2014.
Abstract: Histoplasmosis is a severe infection that affects millions of patients worldwide and is endemic in the Americas. Amphotericin B (AMB) and itraconazole are highly effective for the treatment of severe and milder forms of the disease, but AMB is toxic, and the bioavailability of itraconazole is erratic. Therefore, it is important to investigate new classes of drugs for histoplasmosis treatment. In this study, a series of nine isoniazid hydrazone derivatives were synthesized and evaluated for their antifungal activities in vitro against the dimorphic fungus Histoplasma capsulatum var. capsulatum. The drugs were tested by microdilution in accordance with CLSI guidelines. The compound N=-(1-phenylethylidene)isonicotinohydrazide had the lowest MIC range of all the compounds for the yeast and filamentous forms of H. capsulatum. The in vitro synergy of this compound with AMB against the planktonic and biofilm forms of H. capsulatum cells was assessed by the checkerboard method. The effects of this hydrazone on cellular ergosterol content and membrane integrity were also investigated. The study showed that the compound alone is able to reduce the ergosterol content of planktonic cells and can alter the membrane permeability of the fungus. Furthermore, the compound alone or in combination with AMB showed inhibitory effects against mature biofilms of H. capsulatum. N=-(1-Phenylethylidene)isonicotinohydrazide alone or combined with AMB might be of interest in the management of histoplasmosis.
metadata.dc.type: Artigo
ISSN: 0066-4804 Impresso
1098-6596 On line
Appears in Collections:DSC - Artigos publicados em revista científica

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