4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki-Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies

被引：33

作者：

Cornelio, Benedetta ^{[1
,2
]}

Laronze-Cochard, Marie ^{[1
]}

Ceruso, Mariangela ^{[3
]}

Ferraroni, Marta ^{[3
]}

Rance, Graham A. ^{[4
]}

Carta, Fabrizio ^{[3
]}

Khlobystov, Andrei N. ^{[4
,5
]}

Fontana, Antonella ^{[2
]}

Supuran, Claudiu T. ^{[3
,6
]}

Sapi, Janos ^{[1
]}

机构：

[1] Univ Reims, UFR Pharm, CNRS UMR 7312, Inst Chim Mol Reims, 51 Rue Cognacq Jay, F-51096 Reims, France

[2] Univ G DAnnunzio, Dipartimento Farm, Via Vestini, I-66100 Chieti, Italy

[3] Univ Florence, Dipartimento Chim Ugo Schiff, Via Lastruccia 3, I-150019 Florence, Italy

[4] Univ Nottingham, Sch Chem, Univ Pk, Nottingham NG7 2RD, England

[5] Univ Nottingham, Nottingham Nanotechnol & Nanosci Ctr, Univ Pk, Nottingham NG7 2RD, England

[6] Univ Florence, Neurofarba Dept, Sez Sci Farmaceut & Nutraceut, Via U Schiff 6, I-50019 Florence, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 02期

基金：

欧洲研究理事会;

关键词：

ISOFORM-SELECTIVE INHIBITORS; CROSS-COUPLING REACTIONS; ISOZYME-II; THERAPEUTIC APPLICATIONS; BENZENE SULFONAMIDES; IX; BINDING; POTENT; PATENT; BENZENESULFONAMIDES;

D O I：

10.1021/acs.jmedchem.5b01771

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted arylaryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.

引用

页码：721 / 732

页数：12

共 80 条

[1] Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with EMATE, a dual inhibitor of carbonic anhydrases and steroid sulfatase [J].