4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII

被引：55

作者：

Khloya, Poonam ^{[1
]}

Celik, Gulsah ^{[2
]}

SitaRam ^{[1
]}

Vullo, Daniela ^{[3
]}

Supuran, Claudiu T. ^{[3
,4
]}

Sharma, Pawan K. ^{[1
]}

机构：

[1] Kurukshetra Univ, Dept Chem, Kurukshetra 136119, Haryana, India

[2] Balikesir Univ, Dept Chem, TR-10145 Balikesir, Turkey

[3] Univ Florence, Polo Sci, Lab Chim Bioinorgan, I-50019 Florence, Italy

[4] Univ Florence, Neurofarba Dept, Sect Pharmaceut & Nutraceut Sci, I-50019 Florence, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 76卷

关键词：

Pyrazole; Benzenesulfonamide; Carbonic anhydrase isoforms I; II; IX; XII; Acetazolamide; THERAPEUTIC APPLICATIONS; BIOLOGICAL EVALUATION; SULFONAMIDE; CELECOXIB; AGENTS;

D O I：

10.1016/j.ejmech.2014.02.023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A library of 4-functionalized 1,3-diarylpyrazoles (3a-3h, 5a-5g and 6a-6g) was designed, synthesized and evaluated against four human carbonic anhydrase (CA, EC 4.2.1.1) isozymes representing two cytosolic isozymes hCA I and hCA II, and two transmembrane tumor associated ones, hCA IX and hCA XII. All the twenty two tested compounds exhibited excellent CA activity profile against the four CA isozymes when compared to the reference drug acetazolamide. Six of the tested compounds (3a-3b, 3f, 3h, 6a and 6b) displayed low nanomolar affinity (K-i < 5 nM) for hCA IX whereas seven compounds (3a-3b, 3d-3f, 3h and 6f) displayed K-i < 10 nM against hCA XII. In addition, they acted as selective CA inhibitors of isoforms IX and XII over the physiological isoforms I and II. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：284 / 290

页数：7

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