Article ID Journal Published Year Pages File Type
1372154 Bioorganic & Medicinal Chemistry Letters 2011 4 Pages PDF
Abstract

The complex and highly impermeable cell wall of Mycobacterium tuberculosis (Mtb) is largely responsible for the ability of the mycobacterium to resist the action of chemical therapeutics. An l-rhamnosyl residue, which occupies an important anchoring position in the Mtb cell wall, is an attractive target for novel anti-tuberculosis drugs. In this work, we report a virtual screening (VS) study targeting Mtb dTDP-deoxy-l-lyxo-4-hexulose reductase (RmlD), the last enzyme in the l-rhamnosyl synthesis pathway. Through two rounds of VS, we have identified four RmlD inhibitors with half inhibitory concentrations of 0.9–25 μM, and whole-cell minimum inhibitory concentrations of 20–200 μg/ml. Compared with our previous high throughput screening targeting another enzyme involved in l-rhamnosyl synthesis, virtual screening produced higher hit rates, supporting the use of computational methods in future anti-tuberculosis drug discovery efforts.

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Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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