title: New monomeric and dimeric uridinyl derivatives as inhibitors of chitin synthase.
abstract: This study described the synthesis and in vitro evaluation of eight new derivatives of uridine as antifungal agents and inhibitors of chitin synthase. Dimeric uridinyl derivatives synthesized by us did not exhibit significant activity. One of the studied monomeric derivative, 5'-(N-succinyl)-5'-amino-5'-deoxyuridine methyl ester (compound 7) showed activities against several fungal strains (MIC range 0.06-1.00 mg/mL) and inhibited chitin synthase from Saccharomyces cerevisiae (IC50=0.8mM). Moreover compound 7 exhibited synergistic interaction with caspofungin against Candida albicans (FIC index=0.28).
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kral
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Bieg
authors.affiliation: Department of Pharmaceutical Microbiology and Parasitology, Wroclaw Medical University, Borowska 211A, 50-368 Wrocław, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Nawrot
authors.affiliation: Department of Pharmaceutical Microbiology and Parasitology, Wroclaw Medical University, Borowska 211A, 50-368 Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Włodarczyk
authors.affiliation: Systems Engineering Group, Institute of Automatic Control, Silesian University of Technology, B. Krzywoustego 8, 44-100 Gliwice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lalik
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Hahn
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland. Electronic address: ilona.wandzik@polsl.pl.
authors.forename: Ilona
authors.initials: I
authors.lastname: Wandzik
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001234:Aspergillus niger / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002687:Chitin Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D012233:Rhizopus / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D002687:Chitin Synthase; D014529:Uridine
keywords: Antifungal agents; Chitin synthase inhibitors; Synergism; Uridine