Synthesis of 2,6-dioxo-(1H,3H)-9-N-ribitylpurine and 2,6-dioxo-(1H,3H)-8-aza-9-N-ribitylpurine as inhibitors of lumazine synthase and riboflavin synthase.
2,6-Dioxo-(1H,3H)-9-N-ribitylpurine (6) and 2,6-dioxo-(1H,3H)-8-aza-9-N-ribitylpurine (7) have been synthesized and evaluated as inhibitors of lumazine synthase and riboflavin synthase. Reaction of 5-amino-6-ribitylaminouracil hydrochloride (8) with diethoxymethyl acetate (9) afforded the purine 6, while diazotization of 8 afforded the 8-aza purine 7. Compounds 6 and 7 were evaluated against lumazine synthase of Bacillus subtilis and riboflavin synthase of Escherichia coli. Both 6 and 7 were better inhibitors of lumazine synthase than riboflavin synthase. The 8-azapurine 7 had a lower KI (0.33 and 0.39 mM) than the purine 6 (0.47 and 0.54 mM) when evaluated with lumazine synthase and riboflavin synthase, respectively.
Cushman
M
M
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy, Purdue University, West Lafayette, IN 47907, USA. cushman@pharmacy.purdue.edu
Mavandadi
F
F
Kugelbrey
K
K
Bacher
A
A
D001412:Bacillus subtilis / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D012255:Ribitol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D012258:Riboflavin Synthase / Q000037:antagonists & inhibitors*
C113169:2,6-dioxo-8-aza-9-N-ribitylpurine; C113168:2,6-dioxo-9-N-ribitylpurine; D009097:Multienzyme Complexes; D011687:Purines; D012255:Ribitol; C044822:6,7-dimethyl-8-ribityllumazine synthase; D012258:Riboflavin Synthase