کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10582666 | 981085 | 2011 | 26 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ligand-based modelling followed by synthetic exploration unveil novel glycogen phosphorylase inhibitory leads
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Glycogen phosphorylase (GP) is a valid anti-diabetic target. Accordingly, we applied a drug discovery workflow to unveil novel inhibitory GP leads via combining pharmacophore modeling, QSAR analysis and in silico screening, followed by synthetic exploration of active hits. Virtual screening identified six low micromolar inhibitory leads from the National Cancer Institute (NCI) list of compounds. The most potent hits exhibited anti-GP IC50 values of 3.2 and 4.1 μM. Synthetic exploration of hit 59 (IC50 = 4.1 μM) yielded 25 lead inhibitors with the best illustrating IC50 of 3.0 μM. Interestingly, we prepared several novel mixed oxalyl amide anti-GP leads employing new chemical reaction involving succinic acid-based adducts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 16, 15 August 2011, Pages 4746-4771
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 16, 15 August 2011, Pages 4746-4771
نویسندگان
Maha Habash, Mutasem O. Taha,