2014
DOI: 10.1128/aac.01654-13
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Abstract: f 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 a… Show more

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Cited by 16 publications
(21 citation statements)
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“…However, using isoniazid as the core, chemical structure modification improved its antifungal potential; 3 of 9 isoniazid derivatives had significantly lower MICs against Histoplasma yeasts with one having inhibitory activity at concentrations as low as 7.8 mg/mL. 62 Extending the in vitro tests of the isoniazid-hydrazone derivative to Coccidioides demonstrated it had an MIC of 50 mg/mL against mycelia of this dimorphic fungal pathogen. 87 Although Coccidioides spherules were not tested, there is a reasonable possibility that the MIC will be lower since Histoplasma yeasts were 8-16X more sensitive to the isoniazid-hydrazone than were mycelia.…”
Section: New and Alternative Antifungal Developmentsmentioning
confidence: 99%
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“…However, using isoniazid as the core, chemical structure modification improved its antifungal potential; 3 of 9 isoniazid derivatives had significantly lower MICs against Histoplasma yeasts with one having inhibitory activity at concentrations as low as 7.8 mg/mL. 62 Extending the in vitro tests of the isoniazid-hydrazone derivative to Coccidioides demonstrated it had an MIC of 50 mg/mL against mycelia of this dimorphic fungal pathogen. 87 Although Coccidioides spherules were not tested, there is a reasonable possibility that the MIC will be lower since Histoplasma yeasts were 8-16X more sensitive to the isoniazid-hydrazone than were mycelia.…”
Section: New and Alternative Antifungal Developmentsmentioning
confidence: 99%
“…87 Although Coccidioides spherules were not tested, there is a reasonable possibility that the MIC will be lower since Histoplasma yeasts were 8-16X more sensitive to the isoniazid-hydrazone than were mycelia. 62 Antiretroviral protease inhibitors have inhibitory activity against Histoplasma. Saquinavir is active against both filamentous and yeast forms with an MIC around 0.4 mg/mL.…”
Section: New and Alternative Antifungal Developmentsmentioning
confidence: 99%
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“…However, some of these early reports were based on tests with the filamentous form, and subsequent in vitro susceptibility tests employing the yeast form demonstrated that the Histoplasma yeasts are comparatively resistant to the echinocandins (16,17,20). This morphology-based discrepancy in antifungal susceptibility is not limited to echinocandins and highlights the need to use the most appropriate cell type during antifungal testing (21). With the increasing importance of monitoring antifungal drug resistance and the acceleration of new an-tifungal drug discovery efforts, optimized methods for highthroughput antifungal tests on Histoplasma yeasts are essential.…”
mentioning
confidence: 99%
“…capsulatum [10]. In the present study we have developed isoniazid-derived hydrazones and evaluated their antifungal activity against another dimorphic fungal species, C. posadasii.…”
Section: Introductionmentioning
confidence: 99%