AI Article Synopsis
- Four core structures were studied for their ability to inhibit anthrax lethal factor (LF) while assessing toxicity, physicochemical properties, in vitro ADME profiles, and effectiveness in rat models.
- The phenoxyacetic acid series showed low efficacy in the rat model due to poor stability in rat microsomes and plasma.
- X-ray crystallography uncovered specific interactions that enhance the binding affinity of inhibitors with a secondary amine present in the C2-side chain.
Article Abstract
Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295836 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2012.01.095 | DOI Listing |
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