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Publikācija: 5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with Effective Carbonic Anhydrase Inhibitory Activity: Solution and Crystallographic Investigations

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity Unknown
Defending: ,
Publication language English (en)
Title in original language 5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with Effective Carbonic Anhydrase Inhibitory Activity: Solution and Crystallographic Investigations
Field of research 1. Natural sciences
Sub-field of research 1.4 Chemical sciences
Authors Jekaterīna Ivanova
Agnese Balode
Raivis Žalubovskis
Janis Leitans
Andris Kazaks
Daniela Vullo
Kaspars Tārs
Claudiu T. Supuran
Keywords Carbonic anhydrase, Thiophene-2-sulfonamide, Mercaptan, Inhibitor
Abstract A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromothiophene- 2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar– nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocyclic sulfonamides. as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar– nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocyclic sulfonamides.
DOI: 10.1016/j.bmc.2016.11.045
Hyperlink: http://www.sciencedirect.com/science/article/pii/S0968089616311166?via%3Dihub 
Reference Ivanova, J., Balode, A., Žalubovskis, R., Leitans, J., Kazaks, A., Vullo, D., Tārs, K., Supuran, C. 5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with Effective Carbonic Anhydrase Inhibitory Activity: Solution and Crystallographic Investigations. Bioorganic & Medicinal Chemistry, 2017, Vol.25, No.3, pp.857-863. ISSN 0968-0896. e-ISSN 1464-3391. Available from: doi:10.1016/j.bmc.2016.11.045
Additional information Citation count:
ID 23195