Development of 3-(4-aminosulphonyl)-phenyl-2-mercapto-3-H-quinazolin-4-ones as inhibitors of carbonic anhydrase isoforms involved in tumorigenesis and glaucoma

被引：12

作者：

Alafeefy, Ahmed M. ^{[1
]}

Carta, Fabrizio ^{[2
]}

Ceruso, Mariangela ^{[2
]}

Al-Tamimi, Abdul-Malek S. ^{[3
]}

Al-Kahtani, Abdulla A. ^{[3
,4
]}

Supuran, Claudiu T. ^{[2
,5
]}

机构：

[1] DAIS, BO 217, Alkharj 11981, Saudi Arabia

[2] Univ Florence, Lab Chim Bioinorgan, Polo Sci, Rm 188,Via Lastruccia 3, I-50019 Florence, Italy

[3] Prince Sattam Bin Abdulaziz Univ, Dept Pharmaceut Chem, Coll Pharm, POB 173, Alkharj 11942, Saudi Arabia

[4] King Saud Univ, Dept Chem, Fac Sci, POB 2455, Riyadh 11451, Saudi Arabia

[5] Univ Florence, Sect Pharmaceut & Nutriceut Sci, Neurofarba Dept, Via U Schiff 6, I-50019 Florence, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 06期

关键词：

Carbonic anhydrase; Quinazoline; Sulfonamides; Mercaptan; Tumor-associated isoforms; LOWERING AROMATIC/HETEROCYCLIC SULFONAMIDES; ISOZYME-II; 1,3,5-TRIAZINE MOIETIES; PATHOGENIC BACTERIUM; SELECTIVE INHIBITORS; ZINC-COMPLEXES; DRUG TARGETS; SCHIFF-BASES; PATENT; IX;

D O I：

10.1016/j.bmc.2016.02.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of heterocyclic benzenesulfonamides incorporating 2-mercapto-3H-quinazolin-4-one tails were prepared by condensation of substituted anthranilic acids with 4-isothiocyanato-benzenesulfonamide. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (trans -membrane, tumor-associated enzymes). They acted as medium potency inhibitors of hCA I (K(1)s of 81.0-3084 mu M), being highly effective as hCA II (K(1)s in the range of 0.25-10.8 nM), IX (Kis of 3.7-50.4 nM) and XII (Kis of 0.60-52.9 nM) inhibitors. These compounds should thus be of interest as preclinical candidates in pathologies in which the activity of these enzymes should be inhibited, such as glaucoma (CA II and XII as targets) or some tumors in which the activity of three isoforms (CA II, IX and XII) is dysregulated. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1402 / 1407

页数：6

共 89 条

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