Synthesis and biological evaluation of inhibitors of thymidine monophosphate kinase from Bacillus anthracis.
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.
Byun
Youngjoo
Y
Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Vogel
Susan R
SR
Phipps
Andrew J
AJ
Carnrot
Cecilia
C
Eriksson
Staffan
S
Tiwari
Rohit
R
Tjarks
Werner
W
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
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D013936:Thymidine