title: Tetrazole activity against Candida albicans. The role of KEX2 mutations in the sensitivity to (±)-1-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propan-2-yl acetate.
abstract: Series of 4-(5-aryl-2H-tetrazol-2-yl)butan-2-ol, 1-(5-aryl-2H-tetrazol-2-yl)propan-2-ol and their acetates have been screened against Candida albicans. Among the tested compounds, (±)-1-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propan-2-yl acetate (E5) proved to be the most effective inhibitor of fungal growth and was further evaluated against young (adhesion phase) and mature biofilm in vitro. The activity exhibited by the tested tetrazole derivatives against C. albicans associated with minor cytotoxicity towards Vero epithelial cells make us suggest that E5 could be a promising structure in the development of new antifungals. Serine protease Kex2 appeared essential for the resistance mechanism. Further investigations of in vivo activity, drug interactions, and E5 structure optimization are needed.
authors.affiliation: Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, Warsaw 00-791, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bondaryk
authors.affiliation: Faculty of Chemistry, Institute of Biotechnology, Warsaw University of Technology, Noakowskiego 3, Warsaw 00-664, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Łukowska-Chojnacka
authors.affiliation: Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, Warsaw 00-791, Poland. Electronic address: mstaniszewska@pzh.gov.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Staniszewska
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D002522:Chlorocebus aethiops; D025141:Drug Resistance, Fungal / Q000235:genetics; D005800:Genes, Fungal; D009154:Mutation; D043484:Proprotein Convertases / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry* / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000935:Antifungal Agents; D029701:Saccharomyces cerevisiae Proteins; D013777:Tetrazoles; D043484:Proprotein Convertases; C058751:KEX2 protein, S cerevisiae
keywords: Adhesion; Antifungal activity; Candida albicans; Serine protease Kex2; Tetrazole derivatives