Allylic Selenocyanates as Antifungal Agents Against Pathogenic Candida Species. Issue 34 (8th September 2020)

• Record Type: Journal Article
• Authors: Bazana, Luana C. G.; Carvalho, Ânderson R.; Silveira, Gustavo P.; S. de Oliveira, Luis Flávio; Teixeira, Mário L.; Lopes, William; Vainstein, Marilene H.; Barbosa, Flavio A. R.; Russo, Theo V. C.; Sá, Marcus M.; Canto, Rômulo F. S.; Fuentefria, Alexandre M.
• Is Part Of: ChemistrySelect. Volume 5:Issue 34(2020)
• Page Start: 10495
• Page End: 10500
• Publication Date: 2020-09-08
• Subjects: Allylic Selenocyanate -- Antifungal agents -- Candidiasis -- Cytotoxicity -- Mechanism of action; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202002170
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Candida is a genus that causes the highest number of fungal infections on people around the world, responsible for high mortality rates in critical and immunocompromised patients. Even though several antifungals are commercially available, most of these have side effects or are only available for intravenous administration. In view of this aspect, the susceptibility of twelve allylic selenocyanate (AS) compounds, five of them novel, were tested against 36 Candida strains. The AS were active for all Candida strains reaching minimal inhibitory concentrations (MIC) in the order of ng mL −1 (0.39–50 μg mL −1 ). The sorbitol and ergosterol assay show that these compounds do not act on the cell wall and fungal membrane, suggesting a different mechanism of action. Cytotoxicity and irritability tests showed that only three molecules already studied (2 b, 2 j and 2 i ) for this series manifested damage to the leukocyte cell and chorioallantoic membrane, but at higher concentrations than the MICs. Considering the susceptibility results and parameters of Lipinski, molecules 2 c (0.39–12.5 μg mL −1 ) and 2 d (0.78–6.2 μg mL −1 ) look promising for the development of a new antifungal agent against Candida infections. Abstract : A group of allylic selenocyanates demonstrated good effectiveness against pathogenic Candida spp. isolates. These molecules present a low cytotoxic effect on leukocytes and have no irritability to the chorioallantoic membrane. Electronic micrographs and in vitro tests suggest a different mechanism of action from most commercially available antifungal agents. These findings, combined with low minimal inhibitory concentrations, indicate these compounds as a new promising class of safe antifungal agents.