Inhibition of bacterial dihydrofolate reductase by 6-alkyl-2,4-diaminopyrimidines.

ABSTRACT: (±)-6-Alkyl-2,4-diaminopyrimidine-based inhibitors of bacterial dihydrofolate reductase (DHFR) have been prepared and evaluated for biological potency against Bacillus anthracis and Staphylococcus aureus. Biological studies revealed attenuated activity relative to earlier structures lacking substitution at C6 of the diaminopyrimidine moiety, though minimum inhibitory concentration (MIC) values are in the 0.125-8 μg mL(-1) range for both organisms. This effect was rationalized from three- dimensional X-ray structure studies that indicate the presence of a side pocket containing two water molecules adjacent to the main binding pocket. Because of the hydrophobic nature of the substitutions at C6, the main interactions are with protein residues Leu 20 and Leu 28. These interactions lead to a m

SUBMITTER: Nammalwar B 

PROVIDER: S-EPMC3570588 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature