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Publikācija: 3H-1

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity Unknown
Defending: ,
Publication language English (en)
Title in original language 3H-1,2-Benzoxathiepine 2,2-Dioxides: a New Class of Isoform-Selective Carbonic Anhydrase Inhibitors
Field of research 1. Natural sciences
Sub-field of research 1.4 Chemical sciences
Authors Aleksandrs Pustenko
Dmitrijs Stepanovs
Raivis Žalubovskis
Daniela Vullo
Andris Kazaks
Janis Leitans
Kaspars Tārs
Claudiu Supuran
Keywords Carbonic anhydrase, sulfocoumarin, homo-sulfocoumarins, inhibitor
Abstract A new chemotype with carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action has been discovered, the homo-sulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) which have been designed considering the (sulfo)coumarins as lead molecules. An original synthetic strategy of a panel of such derivatives led to compounds with a unique inhibitory profile and very high selectivity for the inhibition of the tumour associated (CA IX/XII) over the cytosolic (CA I/II) isoforms. Although the CA inhibition mechanism with these new compounds is unknown for the moment, we hypothesize that it may be similar to that of the sulfocoumarins, i.e. hydrolysis to the corresponding sulfonic acids which thereafter anchor to the zinc-coordinated water molecule within the enzyme active site.
DOI: 10.1080/14756366.2017.1316720
Hyperlink: http://www.tandfonline.com/doi/full/10.1080/14756366.2017.1316720 
Reference Pustenko, A., Stepanovs, D., Žalubovskis, R., Vullo, D., Kazaks, A., Leitans, J., Tārs, K., Supuran, C. 3H-1,2-Benzoxathiepine 2,2-Dioxides: a New Class of Isoform-Selective Carbonic Anhydrase Inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, Vol.32, Iss.1, pp.767-775. ISSN 1475-6366. e-ISSN 1475-6374. Available from: doi:10.1080/14756366.2017.1316720
Additional information Citation count:
ID 25566