Open AccessNovel 2-Aryloxazoline Compounds Exhibit an Inhibitory Effect on Candida spp., Including Antifungal-Resistant Isolates
Author(s) -
Luis M. Z. Argomedo,
Vinícius M. Barroso,
Cristiane S. Barreiro,
Mariana P. Darbem,
Kelly Ishida,
Hélio A. Stefani
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00449
Subject(s) - salicylic acid , antifungal , candida infections , microbiology and biotechnology , fungus , minimum inhibitory concentration , aspergillus , candida auris , cytotoxicity , in vitro , cryptococcus , biology , antimicrobial , chemistry , biochemistry , botany
Because of the increased resistance to currently available antifungals, fungal infections represent a significant challenge to human health. Herein, we report the synthesis of 2-aryloxazoline derivatives from the reaction between l-threonine and derivatives of salicylic or naphthoic acid. In total, 26 compounds were obtained and tested against species of Candida , Cryptococcus , and Aspergillus . We found that all of the compounds inhibited the growth of Candida species at low concentrations (<0.25 μg/mL) and exhibited reduced hemolytic and cytotoxic activities. Additionally, compounds 4i and 9i were especially effective against antifungal-resistant isolates and the emerging fungus Candida auris . However, the compounds were less active on Cryptococcus and Aspergillus . Because of the improved in vitro antifungal efficacy and attenuated cytotoxicity, these two 2-aryloxazolines obtained from salicylic and naphthoic acid derivatives, respectively, may be considered lead molecules for the development of novel antifungal drugs.