title: Discovery of bicyclic thymidine analogues as selective and high-affinity inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.
abstract: Thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt) represents an attractive target for selectively blocking bacterial DNA synthesis. Hereby, we report on the discovery of a novel class of bicyclic nucleosides (10 and 11) and one dinucleoside (12), belonging to the most selective inhibitors of TMPKmt discovered so far.
authors.affiliation: Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Vanheusden
authors.forename: Hélène
authors.initials: H
authors.lastname: Munier-Lehmann
authors.forename: Matheus
authors.initials: M
authors.lastname: Froeyen
authors.forename: Roger
authors.initials: R
authors.lastname: Busson
authors.forename: Jef
authors.initials: J
authors.lastname: Rozenski
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C494719:1,3-bis((3'-deoxythymidin-3'-yl)methyl)urea; C494718:1-(3-aminomethyl-2-O-,6-N-carbonyl-3-deoxyribofuranosyl)thymine; C494717:1-(3-aminomethyl-3-deoxy-2-O-,6-N-(thiocarbonyl)ribofuranosyl)thymine; D000995:Antitubercular Agents; D014508:Urea; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D013936:Thymidine