کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1364092 981529 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
QSAR studies for the inhibition of the transmembrane isozymes XII and XIV of human carbonic anhydrase with a series of sulfonamides
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
QSAR studies for the inhibition of the transmembrane isozymes XII and XIV of human carbonic anhydrase with a series of sulfonamides
چکیده انگلیسی

A diverse series of aromatic/heterocyclic sulfonamides possessing inhibitory action against the human transmembrane isoforms XII (cancer-associated) and XIV of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) has been used to develop QSAR models. Including all the 55 investigated sulfonamides in the calibration set, the predictive qualities of the QSAR equations were weak (r2 = 0.1771, F = 5.70) for CA XII and good for CA XIV inhibition (r2 = 0.8222, F = 57.04 before eliminating the outliers, and r2 = 0.8911, F = 67.07 after eliminating them). The obtained models suggest a slightly different inhibition mechanism for the two isoforms. 3-Halogeno-4-amino-benzenesulfonamides were outliers for scaffold hopping for the inhibition of CA XIV. CA XIV inhibitory activity was proportional to the degree of molecular surface rugosity. For compounds of the type X-Ar-SO2NH2 and Ar′-Ar-SO2NH2 type, best inhibitors were detected when Ar/Ar′ incorporates a heterocyclic moiety. These studies may be helpful for the design of more specific CA XII/XIV inhibitors, since this is the first QSAR model investigating them.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 17, 1 September 2007, Pages 5666–5671
نویسندگان
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