Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors

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(2)NH(2)) bearing the 1-benzhydrylpiperazin...

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Detalles Bibliográficos
Autores principales: Berrino, Emanuela, Bua, Silvia, Mori, Mattia, Botta, Maurizio, Murthy, Vallabhaneni S., Vijayakumar, Vijayaparthasarathi, Tamboli, Yasinalli, Bartolucci, Gianluca, Mugelli, Alessandro, Cerbai, Elisabetta, Supuran, Claudiu T., Carta, Fabrizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151984/
https://www.ncbi.nlm.nih.gov/pubmed/28672822
http://dx.doi.org/10.3390/molecules22071049
Descripción
Sumario: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(2)NH(2)) 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 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.

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