کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1379414 982027 2005 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with a library of aromatic and heteroaromatic sulfonamides
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with a library of aromatic and heteroaromatic sulfonamides
چکیده انگلیسی

The inhibition of the two transmembrane, tumor-associated isozymes of carbonic anhydrase (CA, EC 4.2.1.1) of human origin, hCA IX and XII, with a library of aromatic and heteroaromatic sulfonamides has been investigated. Most of them were sulfanilamide, homosulfanilamide, and 4-aminoethyl-benzenesulfonamide derivatives, to which tails that should induce diverse physico-chemical properties have been attached at the amino moiety, whereas several of these compounds were derived from metanilamide, benzene-1,3-disulfonamide or the 1,3,4-thiadiazole/thiadiazoline-2-sulfonamides. The tails were of the alkyl/aryl-carboxamido/sulfonamido-, ureido or thioureido type. Against hCA IX the investigated compounds showed inhibition constants in the range of 3–294 nM, whereas against hCA XII in the range of 1.9–348 nM, respectively. The best hCA IX inhibitors were ureas/thioureas incorporating 4-aminoethyl-benzenesulfonamide and metanilamide moieties. The best hCA XII inhibitors were 1,3,4-thiadiazole/thiadiazoline-2-sulfonamides incorporating 5-acylamido or 5-arylsulfonylamido moieties. These compounds also inhibited appreciably the cytosolic isozymes hCA I and II, but some selectivity for the transmembrane, tumor-associated isozymes was observed for some of them, which is an encouraging result for the design of novel therapies targeting hypoxic tumors, in which these carbonic anhydrases are highly overexpressed.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 21, 1 November 2005, Pages 4862–4866
نویسندگان
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