کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1372154 981866 2011 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel inhibitors of Mycobacterium tuberculosis dTDP-6-deoxy-l-lyxo-4-hexulose reductase (RmlD) identified by virtual screening
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Novel inhibitors of Mycobacterium tuberculosis dTDP-6-deoxy-l-lyxo-4-hexulose reductase (RmlD) identified by virtual screening
چکیده انگلیسی

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.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 23, 1 December 2011, Pages 7064–7067
نویسندگان
, , , , , ,