Title: ProTides of N-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents
Authors: McGuigan, Christopher ×
Derudas, Marco
Gonczy, Blanka
Hinsinger, Karen
Kandil, Sahar
Pertusati, Fabrizio
Serpi, Michaela
Snoeck, Robert
Andrei, Graciela
Balzarini, Jan
McHugh, Timothy D
Maitra, Arundhati
Akorli, Ernest
Evangelopoulos, Dimitrios
Bhakta, Sanjib #
Issue Date: May-2014
Publisher: Pergamon
Series Title: Bioorganic & Medicinal Chemistry vol:22 issue:9 pages:2816-24
Article number: 10.1016/j.bmc.2014.02.056
Abstract: The flavin-dependent thymidylate synthase X (ThyX), rare in eukaryotes and completely absent in humans, is crucial in the metabolism of thymidine (a DNA precursor) in many microorganisms including several human pathogens. Conserved in mycobacteria, including Mycobacterium leprae, and Mycobacterium tuberculosis, it represents a prospective anti-mycobacterial therapeutic target. In a M. tuberculosis ThyX-enzyme inhibition assay, N-(3-(5-(2'-deoxyuridine-5'-phosphate))prop-2-ynyl)octanamide was reported to be the most potent and selective 5-substituted 2'-deoxyuridine monophosphate analogue. In this study, we masked the two charges at the phosphate moiety of this compound using our ProTide technology in order to increase its lipophilicity and then allow permeation through the complex mycobacterial cell wall. A series of N-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide phosphoroamidates were chemically synthesized and their biological activity as potential anti-tuberculars was evaluated. In addition to mycobacteria, several DNA viruses depend on ThyX for their DNA biosynthesis, thus these prodrugs were also screened for their antiviral properties.
ISSN: 0968-0896
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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