ISSN:
0952-3499
Keywords:
glycinamide ribonucleotide formyltransferase (GARFT)
;
nonclassical GARFT inhibitor
;
enamine alkylation
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
Several new 10-formyl and 10-hydroxymethyl derivatives of 5,8,10-trideazapteroic acid have been synthesized by a novel and convenient enamine alkylation procedure. Two of these compounds (10a and 10b) were shown to be very powerful inhibitors of L. casei (10a, IC50 = 8 × 10-6 M; 10b, IC50 = 7 × 10-6 M) and recombinant mouse (10a, IC50 = 3.4 × 10-5 M; 10b, IC50 = 2.8 × 10-5 M) glycinamide ribonucleotide formyltransferase (GARFT). These IC50 values are comparable to the classical GARFT inhibitor (6R)-DDATHF (IC50, L. casei 2.3 × 10-6M; recombinant mouse 2.3 × 10-5 M) under identical assay conditions. For both compounds, the inhibition of L. casei GARFT increased with time of incubation, but not markedly with the recombinant mouse enzyme. Due to their potential ability to interfere with purine biosynthesis and to penetrate microbial cells the new nonclassical GARFT inhibitors reported here may be useful for the treatment of infections caused by microorganisms that are sensitive and resistant to conventional antimicrobial agents.
Additional Material:
1 Ill.
Type of Medium:
Electronic Resource
