5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations

Jekaterīna Ivanova; Agnese Balode; Raivis Žalubovskis; Janis Leitans; Andris Kazaks; Daniela Vullo; Kaspars Tars; Claudiu T. Supuran

doi:10.1016/j.bmc.2016.11.045

5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations

Jekaterīna Ivanova
, Agnese Balode
, Raivis Žalubovskis^*
, Janis Leitans
, Andris Kazaks
, Daniela Vullo
, Kaspars Tars
, Claudiu T. Supuran

^*Corresponding author for this work

Department of Molecular Life Sciences, Microbiology and Biotechnology

Latvian Institute of Organic Synthesis
Riga Technical University
Latvian Biomedical Research and Study Centre
University of Florence

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-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 (K_Is 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.

Original language	English
Pages (from-to)	857-863
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	25
Issue number	3
DOIs	https://doi.org/10.1016/j.bmc.2016.11.045
Publication status	Published - 2017

Keywords

Carbonic anhydrase
Inhibitor
Mercaptan
Thiophene-2-sulfonamide

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title = "5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations",

abstract = "A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-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.",

keywords = "Carbonic anhydrase, Inhibitor, Mercaptan, Thiophene-2-sulfonamide",

author = "Jekaterīna Ivanova and Agnese Balode and Raivis {\v Z}alubovskis and Janis Leitans and Andris Kazaks and Daniela Vullo and Kaspars Tars and Supuran, \{Claudiu T.\}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd",

year = "2017",

doi = "10.1016/j.bmc.2016.11.045",

language = "English",

volume = "25",

pages = "857--863",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

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T1 - 5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity

T2 - Solution and crystallographic investigations

AU - Ivanova, Jekaterīna

AU - Balode, Agnese

AU - Žalubovskis, Raivis

AU - Leitans, Janis

AU - Kazaks, Andris

AU - Vullo, Daniela

AU - Tars, Kaspars

AU - Supuran, Claudiu T.

PY - 2017

Y1 - 2017

N2 - A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-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.

AB - A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-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.

KW - Carbonic anhydrase

KW - Inhibitor

KW - Mercaptan

KW - Thiophene-2-sulfonamide

UR - https://www.scopus.com/pages/publications/85009259836

U2 - 10.1016/j.bmc.2016.11.045

DO - 10.1016/j.bmc.2016.11.045

M3 - Article

C2 - 28024887

AN - SCOPUS:85009259836

SN - 0968-0896

VL - 25

SP - 857

EP - 863

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 3

ER -

5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations

Abstract

Keywords

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