کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10582758 981101 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular modeling based approach, synthesis and in vitro assay to new indole inhibitors of hepatitis C NS3/4A serine protease
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Molecular modeling based approach, synthesis and in vitro assay to new indole inhibitors of hepatitis C NS3/4A serine protease
چکیده انگلیسی
In an attempt to identify potential HCV NS3 protease inhibitors lead compounds, a series of novel indoles (10a-g) was designed. Molecular modeling study, including fitting to a 3D-pharmacophore model of the designed molecules (10a-g), with HCV NS3 protease hypothesis using catalyst program was fulfilled. Also, the molecular docking into the NS3 active site was examined using Discovery Studio 2.5 software. Several compounds showed significant high simulation docking score and fit values. The designed compounds with high docking score and fit values were synthesized and biologically evaluated in vitro using an NS3 protease binding assay. It appears that most of the tested compounds reveal promising inhibitory activity against NS3 protease. Of these, compounds 10a and 10b demonstrated potent HCV NS3 protease inhibitors with IC50 values of 9 and 12 μg/mL, respectively. The experimental serine protease inhibitor activities of compounds 10a-g were consistent with their molecular modeling results. Inhibitors from this class have promising characteristics for further development as anti-HCV agents.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 1, 1 January 2011, Pages 374-383
نویسندگان
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