کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1395696 1501229 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure-based pharmacophore of COX-2 selective inhibitors and identification of original lead compounds from 3D database searching method
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure-based pharmacophore of COX-2 selective inhibitors and identification of original lead compounds from 3D database searching method
چکیده انگلیسی

A four-point pharmacophore of COX-2 selective inhibitors was derived from a training set of 16 compounds, using the Catalyst program. It consists of a H bond acceptor, two hydrophobic groups and an aromatic ring, in accordance with SAR data of the compounds and with topology of the COX-2 active site. This hypothesis, combined with exclusion volume spheres representing important residues of the COX-2 binding site, was used to virtually screen the Maybridge database. Eight compounds were selected for an in vitro enzymatic assay. Five of them show COX-2 inhibition close to that of nimesulide and rofecoxib, two reference COX-2 selective inhibitors. As a result, structure-based pharmacophore generation was able to identify original lead compounds, inhibiting the COX-2 isoform.

A structure-based four-point pharmacophore of COX-2 selective inhibitors was used to screen the Maybridge database and allowed to identify two original molecules with a new scaffold.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 41, Issue 12, December 2006, Pages 1446–1455
نویسندگان
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