کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1372154 | 981866 | 2011 | 4 صفحه PDF | دانلود رایگان |

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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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 23, 1 December 2011, Pages 7064–7067