Central nervous system distributional kinetics of selected histone deacetylase inhibitors.

Histone deacetylase expression and activity are often dysregulated in central nervous system (CNS) tumors, providing a rationale for investigating histone deacetylase inhibitors (HDACIs) in selected brain tumor patients. Although many HDACIs have shown potential in in vitro studies, they have had modest efficacy in vivo. This lack of activity could be due to insufficient CNS exposure to the unbound drug.

Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.

Protecting Group Control of Hydroxyketone-Hemiketal Tautomeric Equilibrium Enables the Stereoselective Synthesis of a 1-Azido -Nucleoside.

The synthesis of 1-azido -nucleosides is described to expand the set of azide-functionalized nucleosides for bioorthogonal applications and as potential antiviral drugs. Lewis acid-promoted azidation of a nucleoside hemiketal resulted in the formation of a tetrazole through a Schmidt reaction manifold. Conformational control to prevent ring-chain tautomerism enabled efficient 1-azidation with complete β-diastereoselectivity.

Evaluation of corn fermented protein on the fecal microbiome of cats.

Co-products from the ethanol industry, such as distillers dried grains with solubles (DDGS), can provide alternative protein sources for pet food. Corn fermented protein (CFP) is produced using postfermentation technology to split the protein and yeast from fiber prior to drying. This results in a higher protein ingredient compared to DDGS, increasing its appeal for pet food.