title: The synthesis and antifungal activity of (20S)-3β-acetoxy-5α-pregnane-20,16β-carbolactone against fluconazole - Resistant Candida cells.
abstract: An efficient procedure for the synthesis of (20S)-3β-acetoxy-5α-pregnane-20,16β-carbolactone is described. Bactericidal and fungicidal activity of the lactone against different bacteria such as MSSA, MRSA, E. coli ESBL, P. aeruginosa and clinical isolates of Candida spp., in planktonic and biofilm growth stage were assessed. Additionally, the affinity of this new compound to microbial plasma membrane and hemoglobin release from human red blood cells were determined using fluorometric and colorimetric assay, respectively. Our studies revealed that the lactone exhibits strong antifungal activity, and the ability to prevent pathogens' biofilm formation. Additionally, upon lactone treatment a significant affinity to fungal, but not to human cell membranes, indicating suitable biocompatibility was observed.
authors.affiliation: Institute of Chemistry, University of Białystok, ul. Ciołkowskiego 1K, 15-245 Białystok, Poland. Electronic address: gierdas@uwb.edu.pl.
authors.forename: Izabella
authors.initials: I
authors.lastname: Jastrzebska
authors.affiliation: Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok, ul. Mickiewicza 2C, 15-222 Bialystok, Poland. Electronic address: katarzyna.niemirowicz@umb.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Niemirowicz
authors.affiliation: Institute of Chemistry, University of Białystok, ul. Ciołkowskiego 1K, 15-245 Białystok, Poland.
authors.forename: Wioleta I
authors.initials: WI
authors.lastname: Brzozowska
authors.affiliation: Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok, ul. Mickiewicza 2C, 15-222 Bialystok, Poland; Department of Physiology, Pathophysiology and Microbiology of Infections, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, ul. IX Wieków Kielc 19, Kielce, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Bucki
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole
keywords: Antibacterial activity; Antifungal activity; Bisnorcholanic lactone; Outer membrane disruption