- Synthesis and antifungal activity in vitro of isoniazid Derivatives against histoplasma capsulatum var. Capsulatum
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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. Copyright
- De Aguiar Cordeiro, Rossana,De Farias Marques, Francisca Jakelyne,De Aguiar Cordeiro, Rebecca,Da Silva, Marcos Reinaldo,Malaquias, Angela Donato Maia,De Melo, Charlline Vládia Silva,Mafezoli, Jair,De Oliveira, Maria Da Concei??o Ferreira,Brilhante, Raimunda Samia Nogueira,Rocha, Marcos Fábio Gadelha,De Jesus Pinheiro Gomes Bandeira, Tereza,Sidrima, José Júlio Costa
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p. 2504 - 2511
(2014/05/06)
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- Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of isonicotinic acid-1-(substituted phenyl)-ethylidene/cycloheptylidene hydrazides
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A series of isonicotinic acid-1-(substituted phenyl)-ethylidene/ cycloheptylidene hydrazide derivatives (1-12) was tested for their, in vitro antimycobacterial activity against Mycobacterium tuberculosis, and compound 2 was found to be more active than isoniazid. The antiviral screening results indicated that none of the tested compounds was active against a broad variety of DNA and RNA viruses at subtoxic concentrations, except compounds 8 and 10 that proved to be active against DNA viruses at concentrations close to their cytostatic potential. The synthesized compounds were also screened for their antimicrobial potential against S. aureus, B. subtilis, E. coli, C. albicans and A. niger, and the results indicated that compounds having Br, OCH3 and Cl groups were highly active. The multi-target QSAR models indicated the importance of lipophilic (log P) and topological parameters (3vv) in describing the antimicrobial activity.
- Judge, Vikramjeet,Ahuja, Munish,Narasimhan, Balasubramanian,Sriram, Dharmarajan,Yogeeswari, Perumal,De Clercq, Erik,Pannecouque, Christophe,Balzarini, Jan
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p. 1935 - 1952,18
(2020/07/30)
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