Synthesis and Biological Evaluation of Hydrazone Derivatives as Antifungal Agents

Molecules

Bruna B. Casanova³  Mauro N. Muniz³  Thayse de Oliveira²  Luís Flavio de Oliveira¹  Michel M. Machado¹  Alexandre M. Fuentefria²  Grace Gosmann³  Simone C. B. Gnoatto³ 

[1] Departamento de Farmácia, Universidade Federal do Pampa, Km 592, Uruguaiana 97500-970, RS, Brazil; E-Mails:;Laboratório de Micologia Aplicada, Departamento de Analises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90610-000, RS, Brazil; E-Mails:;Laboratório de Fitoquímica e Síntese Orgânica (LAFIS), Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90610-000, RS, Brazil; E-Mails:

关键词: aldehydes;    hydrazones;    emerging yeasts;    antifungal activity;   

DOI  :  10.3390/molecules20059229

来源: mdpi

【 摘 要 】

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16–32 μg/mL and 8–16 μg/mL, respectively. The compounds’ action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.