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New monomeric and dimeric uridinyl derivatives as inhibitors of chitin synthase
Affiliation:1. Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland;2. Department of Pharmaceutical Microbiology and Parasitology, Wroclaw Medical University, Borowska 211A, 50-368 Wrocław, Poland;3. Systems Engineering Group, Institute of Automatic Control, Silesian University of Technology, B. Krzywoustego 8, 44-100 Gliwice, Poland;1. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China;2. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China;1. International Atomic Energy Agency (IAEA), IAEA Laboratories, Nuclear Science and Instrumentation Laboratory, A-2444 Seibersdorf, Austria;2. Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2-12, 10587 Berlin, Germany;3. Ruđer Bošković Institute (RBI), Zagreb, Croatia;4. Helmholtz-Zentrum Berlin für Materialien und Energie GmbH (HZB), Hahn-Meitner-Platz 1, 14109 Berlin, Germany;5. Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, E. N. 10, Apartado 21, 2686-953 Sacavém, Portugal;6. Institute of Nuclear and Particle Physics, NCSR “Demokritos”, 153 10 Aghia Paraskevi, Athens Greece;1. Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand;2. Biomolecular Interaction Centre, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand;1. Institute of Nanotechnology and Microsystems Engineering, National Cheng Kung University, 701 Tainan, Taiwan, ROC;2. Institute of Microelectronics, Department of Electrical Engineering, Advanced Optoelectronic Technology Center, National Cheng Kung University, 701 Tainan, Taiwan, ROC
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 = 0.8 mM). Moreover compound 7 exhibited synergistic interaction with caspofungin against Candida albicans (FIC index = 0.28).
Keywords:Uridine  Chitin synthase inhibitors  Antifungal agents  Synergism
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