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Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors.

ABSTRACT: The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO?NH?) bearing the 1-benzhydrylpiperazine tail and connected by means of a ?-alanyl or nipecotyl spacer. All compounds 6a-l were investigated in vitro for their ability to inhibit the physiological relevant human (h) CA isoforms such as I, II, IV and IX. Molecular modeling provided further structural support to enzyme inhibition data and structure-activity relationship. In conclusion the hCA I resulted the most inhibited isoform, whereas all the remaining ones showed different inhibition profiles.

SUBMITTER: Berrino E

PROVIDER: S-EPMC6151984 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors.

Berrino Emanuela E Bua Silvia S Mori Mattia M Botta Maurizio M Murthy Vallabhaneni S VS Vijayakumar Vijayaparthasarathi V Tamboli Yasinalli Y Bartolucci Gianluca G Mugelli Alessandro A Cerbai Elisabetta E Supuran Claudiu T CT Carta Fabrizio F

Molecules (Basel, Switzerland) 20170624 7

The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO₂NH₂) bearing the 1-benzhydrylpiperazine tail and connected by means of a β-alanyl or nipecotyl spacer. All compounds 6a-l were investigated in vitro for their ability to inhibit the physiological relevant human (h) CA isoforms s ...[more]

PMID: 28672822

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