Sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen Porphyromonas gingivalis

被引：51

作者：

Vullo, Daniela ^{[1
]}

Del Prete, Sonia ^{[2
,3
]}

Osman, Sameh M. ^{[4
]}

De Luca, Viviana ^{[2
,3
]}

Scozzafava, Andrea ^{[1
]}

AlOthman, Zeid ^{[4
]}

Supuran, Claudiu T. ^{[1
,4
,5
]}

Capasso, Clemente ^{[2
,3
]}

机构：

[1] Univ Florence, Chim Bioorgan Lab, I-50019 Florence, Italy

[2] CNR, Ist Biochim Prot, I-80131 Naples, Italy

[3] CNR, Inst Biosci & Bioresources IBBR, I-80131 Naples, Italy

[4] King Saud Univ, Coll Sci, Dept Chem, Riyadh 11451, Saudi Arabia

[5] Univ Florence, Dipartimento NEIROFABA, Sez Sci Farmaceut & Nutraceut, I-50019 Florence, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 01期

关键词：

Carbonic anhydrase; Gamma-class enzyme; Sulfonamide; Porphyromonas gingivalis; CLASS ENZYME; BETA; GINGIPAINS; VIRULENCE; BENZENESULFONAMIDES; ANTICANCER; MECHANISM; ACTIVATION; ISOENZYMES; PARASITE;

D O I：

10.1016/j.bmcl.2013.11.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A carbonic anhydrase (CA, EC 4.2.1.1) denominated PgiCA, belonging to the gamma-class, from the oral pathogenic bacteria Porphyromonas gingivalis, the main causative agent of periodontitis, was investigated for its inhibition profile with sulfonamides and one sulfamate. Dichlorophenamide, topiramate and many simple aromatic/ heterocyclic sulfonamides were ineffective as PgiCA inhibitors whereas the best inhibition was observed with halogenosulfanilamides incorporating heavy halogens, 4-hydroxy-and 4-hydroxyalkyl- benzenesulfonamides, acetazolamide, methazolamide, zonisamide, indisulam, celecoxib, saccharin and hydrochlorothiazide (K(I)s in the range of 131-380 nM). The inhibition profile of PgiCA was very different from that of CAM, hCA I and II or the beta-CA from a protozoan parasite (Leishmania donovani chagasii). Identification of potent and possibly selective inhibitors of PgiCA may lead to pharmacological tools useful for understanding the physiological role(s) of this enzyme. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：240 / 244

页数：5

共 51 条

[1] Bacteria of dental caries in primary and permanent teeth in children and young adults [J].