کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361429 981463 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity
چکیده انگلیسی

Compounds that bind at the colchicine site of tubulin have drawn considerable attention with studies indicating that these agents suppress microtubule dynamics and inhibit tubulin polymerization. Data for 18 polysubstituted pyrrole compounds are reported, including antiproliferative activity against human MDA-MB-435 cells and calculated free energies of binding following docking the compounds into models of αβ-tubulin. These docking calculations coupled with HINT interaction analyses are able to represent the complex structures and the binding modes of inhibitors such that calculated and measured free energies of binding correlate with an r2 of 0.76. Structural analysis of the binding pocket identifies important intermolecular contacts that mediate binding. As seen experimentally, the complex with JG-03-14 (3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester) is the most stable. These results illuminate the binding process and should be valuable in the design of new pyrrole-based colchicine site inhibitors as these compounds have very accessible syntheses.

HINT Interaction maps of JG-03-14 bound at the colchicine site of tubulin. Blue contours: favorable polar (H-bond); red: unfavorable polar; green: hydrophobic.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 5, 1 March 2008, Pages 2235–2242
نویسندگان
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