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2000
Volume 25, Issue 19
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Aim

The present study aims to identify the synthesis and structural characterization of acyl hydrazone-sulfonamide-containing compounds that were tested on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII.

Methods

Herein, acyl hydrazone derivatives containing the primary sulfonamide moiety were synthesized a three-step synthetic pathway starting from the commercially available 4-sulfamoyl benzoic acid. Structural characterizations of the final compounds were assessed through IR IR, 1H-NMR, 13C-NMR, and elemental analyses. The profiling activity of the final compounds on the Carbonic Anhydrases (CAs; EC 4.2.1.1) I, II, IX, and XII were performed by means of the stopped-flow technique and revealed nanomolar inhibitory potencies on the selected targets. Molecular docking and molecular dynamic simulations afforded a detailed understanding of the binding modes of the most effective compounds.

Results

We reported the synthesis and structural characterization of 25 acyl hydrazone-sulfonamide-containing compounds that were tested on the hCAs I, II, IX, and XII isoforms for their inhibitory features. Overall, all compounds showed nanomolar inhibition potencies on the panel of hCAs considered, and their binding modes were deciphered by means of studies. Molecular docking followed by MD simulations confirmed the stability of -hCA I, -hCA II, -hCA II, -hCA XII, and -hCA XII complexes.

Conclusion

This study presents a deep understanding of the structural determinants influencing the affinity and selectivity of the designed compounds towards different hCAs, thus offering valuable insights for further optimization and development in the field.

© 2025 Bentham Science Publishers
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2025-02-25
2025-10-21

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Preliminary Investigations on Acyl Hydrazones Bearing Sulfonamides as Inhibitors of the Human Carbonic Anhydrase Isoforms I, II, IX, and XII
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 1521 (2025); https://doi.org/10.2174/0118715206356980250113074705
/content/journals/acamc/10.2174/0118715206356980250113074705
/content/journals/acamc/10.2174/0118715206356980250113074705
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  • Article Type:     Research Article
Keyword(s): acyl hydrazones; in-silico; molecular docking; molecular dynamic simulations; sulfonamides; Synthesis

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