Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase.

ABSTRACT:

Background

Bacterial resistance to antibiotic therapies is increasing and new treatment options are badly needed. There is an overlap between these resistant bacteria and organisms classified as likely bioterror weapons. For example, Bacillus anthracis is innately resistant to the anti-folate trimethoprim due to sequence changes found in the dihydrofolate reductase enzyme. Development of new inhibitors provides an opportunity to enhance the current arsenal of anti-folate antibiotics while also expanding the coverage of the anti-folate class.

Methods

We have characterized inhibitors of B. anthracis dihydrofolate reductase by measuring the K(i) and MIC values and calculating the energetics of binding. This series contains a core diaminopyrimidine ring, a central dimethoxybenzy

SUBMITTER: Bourne CR 

PROVIDER: S-EPMC3530638 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature