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Publikācija: N-Substituted and Ring Opened Saccharin Derivatives Selectively Inhibit Transmembrane

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity State funding for education
Defending: ,
Publication language English (en)
Title in original language N-Substituted and Ring Opened Saccharin Derivatives Selectively Inhibit Transmembrane, Tumor-Associated Carbonic Anhydrases IX and XII
Field of research 1. Natural sciences
Sub-field of research 1.4 Chemical sciences
Authors Jekaterīna Ivanova
Fabrizio Carta
Daniela Vullo
Janis Leitans
Andris Kazaks
Kaspars Tārs
Raivis Žalubovskis
Claudiu T. Supuran
Keywords Carbonic anhydrase | Inhibitor | Isoform selectivity | Saccharin | Secondary/tertiary sulfonamide
Abstract A series of N-substituted saccharins incorporating aryl, alkyl and alkynyl moieties, as well as some ring opened derivatives were prepared and investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The widespread cytosolic isoforms CA I and II were not inhibited by these sulfonamides whereas transmembrane, tumor-associated ones were effectively inhibited, with K I s in the range of 22.1–481 nM for CA IX and of 3.9–245 nM for hCA XII. Although the inhibition mechanism of these tertiary/secondary sulfonamides is unknown for the moment, the good efficacy and especially selectivity for the inhibition of the tumor-associated over the cytosolic, widespread isoforms, make these derivatives of considerable interest as enzyme inhibitors with various pharmacologic applications.
DOI: 10.1016/j.bmc.2017.04.007
Hyperlink: http://www.sciencedirect.com/science/article/pii/S0968089617305254?via%3Dihub 
Reference Ivanova, J., Carta, F., Vullo, D., Leitans, J., Kazaks, A., Tārs, K., Žalubovskis, R., Supuran, C. N-Substituted and Ring Opened Saccharin Derivatives Selectively Inhibit Transmembrane, Tumor-Associated Carbonic Anhydrases IX and XII. Bioorganic and Medicinal Chemistry, 2017, Vol.25, No.13, pp.3583-3589. ISSN 0968-0896. Available from: doi:10.1016/j.bmc.2017.04.007
Additional information Citation count:
ID 26427