Poly(amidoamine) Dendrimers with Carbonic Anhydrase Inhibitory Activity and Antiglaucoma Action

被引：33

作者：

Carta, Fabrizio ^{[1
]}

Osman, Sameh M. ^{[2
]}

Vullo, Daniela ^{[1
]}

Gullotto, Antonella ^{[1
]}

Winum, Jean-Yves ^{[3
]}

AlOthman, Zeid ^{[2
]}

Masini, Emanuela ^{[4
]}

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

机构：

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

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

[3] Univ Montpellier, CNRS ENSCM, IBMM, Ecole Natl Super Chim Montpellier,UMR 5247, F-34296 Montpellier, France

[4] Univ Florence, Sez Farmacol, Dipartimento NEUROFARBA, I-50139 Florence, Italy

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 09期

关键词：

PATHOGEN PORPHYROMONAS-GINGIVALIS; BIOMEDICAL APPLICATIONS; SULFONAMIDE INHIBITION; PAMAM DENDRIMERS; DRUG-DELIVERY; PATENT; CELLS; ACTIVATORS; COUMARINS; DISCOVERY;

D O I：

10.1021/acs.jmedchem.5b00383

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Four generations of poly(amidoamine) (PAMAM) dendrimers decorated with benzenesulfonamide moieties were prepared by derivatizing the amino groups of the dendrimer with 4-carboxy-benzenesulfonamide functionalities. Compounds incorporating 4, 8, 16, and 32 sulfonamide moieties were thus obtained, which showed an increasing carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action with the increase of the number of sulfamoyl groups in the dendrimer. Best inhibitory activity (in the low nanomolar-subnanomolar range) was observed for isoforms CA II and XII, involved among others in glaucoma. In an animal model of this disease, the chronic administration of such dendrimers for 5 days led to a much more efficient drop of intraocular pressure compared to the standard drug dorzolamide.

引用

页码：4039 / 4045

页数：7

共 53 条

[1]

Anticonvulsant/antiepileptic carbonic anhydrase inhibitors: a patent review [J].