RTU Research Information System
Latviešu English

Publikācija: Hydrophobic Substituents of the Phenylmethylsulfamide Moiety Can Be Used for the Development of New Selective Carbonic Anhydrase Inhibitors

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity Unknown
Defending: ,
Publication language English (en)
Title in original language Hydrophobic Substituents of the Phenylmethylsulfamide Moiety Can Be Used for the Development of New Selective Carbonic Anhydrase Inhibitors
Field of research 1. Natural sciences
Sub-field of research 1.4 Chemical sciences
Authors Jekaterīna Ivanova
Raivis Žalubovskis
Ginta Pizika
Simona Maria Monti
Giuseppina De Simone
Anna Di Fiore
Igor Vozny
Peteris Trapencieris
Claudiu T. Supuran
Vincenzo Alterio
Keywords
Abstract A new series of compounds containing a sulfamide moiety as zinc-binding group (ZBG) has been synthesized and tested for determining inhibitory properties against four human carbonic anhydrase (hCA) isoforms, namely, CAs I, II, IX, and XII. The X-ray structure of the cytosolic dominant isoform hCA II in complex with the best inhibitor of the series has also been determined providing further insights into sulfamide binding mechanism and confirming that such zinc-binding group, if opportunely derivatized, can be usefully exploited for obtaining new potent and selective CAIs. The analysis of the structure also suggests that for drug design purposes the but-2-yn-1-yloxy moiety tail emerges as a very interesting substituent of the phenylmethylsulfamide moiety due to its capability to establish strong van der Waals interactions with a hydrophobic cleft on the hCA II surface, delimited by residues Phe131, Val135, Pro202, and Leu204. Indeed, the complementarity of this tail with the cleft suggests that different substituents could be used to discriminate between isoforms having clefts with different sizes.
DOI: 10.1155/2014/523210
Hyperlink: https://www.hindawi.com/journals/bmri/2014/523210/ 
Reference Ivanova, J., Žalubovskis, R., Pizika, G., Monti, S., De Simone, G., Di Fiore, A., Vozny, I., Trapencieris, P., Supuran, C., Alterio, V. Hydrophobic Substituents of the Phenylmethylsulfamide Moiety Can Be Used for the Development of New Selective Carbonic Anhydrase Inhibitors. BioMed Research International, 2014, Vol.2014, pp.1-11. ISSN 2314-6133. Available from: doi:10.1155/2014/523210
Additional information Citation count:
ID 24036