Click Chemistry-Enabled Parallel Synthesis of N-Acyl Sulfonamides and Their Evaluation as Carbonic Anhydrase Inhibitors

A synthetically accessible library of <i>N</i>-acyl sulfonamides was constructed using a combination of copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and <i>N</i>-acylation of primary sulfonamides. The proposed two-step reaction sequence had a high experimentally confirmed synthetic success rate (up to 85%) and gave reasonable product yields (up to 61%). As a result of the validation process, a 262-member compound library (out of >70K accessible combinations) was prepared. Biological profiling of the synthesized library by differential scanning fluorimetry and enzymatic assays identified several low micromolar inhibitors of human carbonic anhydrase. The interaction of the discovered hits with the biological target was studied by docking and molecular dynamics.

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Publication Details

Journal
Molecules
Published
2026-01-16
DOI
https://doi.org/10.3390/molecules31020318
Primary Topic
Enzyme function and inhibition
Type
article
Field-Weighted Citation Impact
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article

Click Chemistry-Enabled Parallel Synthesis of N-Acyl Sulfonamides and Their Evaluation as Carbonic Anhydrase Inhibitors

Anzhelika I. Konovets, Vasyl Naumchyk, В. С. Броварец, Olga Kuchuk et al.
Molecules
Enzyme function and inhibition
article

Click Chemistry-Enabled Parallel Synthesis of N-Acyl Sulfonamides and Their Evaluation as Carbonic Anhydrase Inhibitors

Anzhelika I. Konovets, Vasyl Naumchyk, В. С. Броварец, Olga Kuchuk, Oleksandr O. Grygorenko, A. P. Pogribna, S.O. Nikitin, Sergey Zozulya, Oleksii Hrabovskyi, Dmytro S. Radchenko, Bohdan V. Vashchenko, Oleksii Chuk, Oleksii Gavrylenko, Bohdan S. Sosunovych, Yurii S. Moroz
article en

Abstract

A synthetically accessible library of <i>N</i>-acyl sulfonamides was constructed using a combination of copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and <i>N</i>-acylation of primary sulfonamides. The proposed two-step reaction sequence had a high experimentally confirmed synthetic success rate (up to 85%) and gave reasonable product yields (up to 61%). As a result of the validation process, a 262-member compound library (out of >70K accessible combinations) was prepared. Biological profiling of the synthesized library by differential scanning fluorimetry and enzymatic assays identified several low micromolar inhibitors of human carbonic anhydrase. The interaction of the discovered hits with the biological target was studied by docking and molecular dynamics.

MoleculesVol. 31(2)
Taras Shevchenko National University of Kyiv (UA), Institute of Bioorganic Chemistry and Petrochemistry V.P. Kukhar (UA), Winston Churchill Foundation (US), Palladin Institute of Biochemistry (UA), Enamine (Ukraine) (UA), Institute of Molecular Biology and Genetics (UA)
Openalex Percentile: Top 87%
Enzyme function and inhibition
DOIOpen Access PDFOpenAlex
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