کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1396244 1501183 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
3D-QSAR pharmacophore modeling and in silico screening of new Bcl-xl inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
3D-QSAR pharmacophore modeling and in silico screening of new Bcl-xl inhibitors
چکیده انگلیسی

Bcl-2 proteins family members play several roles in tumoral proliferation: they inhibit proapoptotic activity during oncogenesis, support tumor cells survival, induce chemoresistance. The discovery of new small inhibitors of Bcl-xl represents a new frontier for cancer treatment. In this study, a 3D-QSAR pharmacophore model was developed, based on 42 biarylacylsulfonamides, and used to understand the structural factors affecting the inhibitory potency of these derivatives. Aromatic, negative charge, and hydrogen bond acceptor effects contribute to the inhibitory activity. The model was then employed as 3D search query to screen ZINC drug-like database in order to select new scaffolds. Finally six hits were identified. Docking study evidenced the capability of these compounds to interact with Bcl-xl receptor, and they were selected for further in vitro and in vivo assay studies.

A 3D-QSAR pharmacophore model was developed, based on 42 biarylacylsulfonamides, and used to understand the structural factors affecting the inhibitory activity.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 45, Issue 11, November 2010, Pages 4774–4782
نویسندگان
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