title: Synthesis and biological evaluation of inhibitors of thymidine monophosphate kinase from Bacillus anthracis.
abstract: Nineteen lipophilic thymidine phosphate-mimicking compounds were designed and synthesized as potential inhibitors of thymidine monophosphate kinase of Bacillus anthracis, a Gram-positive bacterium that causes anthrax. These thymidine analogues were substituted at the 5'-postion with sulfonamide-, amide-, (thio)urea-, or triazole groups, which served as lipophilic surrogates for phosphate. Three of the tested compounds produced inhibition of B. anthracis Sterne growth and/or thymidine monophosphate activity. Additional studies will be necessary to elucidate the potential of this type of B. anthracis thymidine monophosphate inhibitors as novel antibiotics in the treatment of anthrax.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Susan R
authors.initials: SR
authors.lastname: Vogel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Phipps
authors.forename: Cecilia
authors.initials: C
authors.lastname: Carnrot
authors.forename: Staffan
authors.initials: S
authors.lastname: Eriksson
authors.forename: Rohit
authors.initials: R
authors.lastname: Tiwari
authors.forename: Werner
authors.initials: W
authors.lastname: Tjarks
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001408:Bacillus anthracis / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D013936:Thymidine