Preliminary Investigations on Acyl Hydrazones Bearing Sulfonamides as Inhibitors of the Human Carbonic Anhydrase Isoforms I, II, IX, and XII


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Abstract

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

Methods:Herein, acyl hydrazone derivatives containing the primary sulfonamide moiety were synthesized via 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 in vitro 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 in vitro 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 in-silico studies. Molecular docking followed by MD simulations confirmed the stability of 4l-hCA I, 4n-hCA II, 4t-hCA II, 4v-hCA XII, and 4w-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.

About the authors

Efe Dogukan Dincel

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University

Author for correspondence.
Email: info@benthamscience.net

Ebru Didem Kuran

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University

Email: info@benthamscience.net

Abdulilah Ece

Department of Medical Biochemistry, Faculty of Medicine, Biruni University

Author for correspondence.
Email: info@benthamscience.net

Faika Basoglu-Unal

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, European University of Lefke

Email: info@benthamscience.net

Gioele Renzi

Neurofarba Department, University of Florence, Section of Pharmaceutical and Nutraceutical Sciences

Email: info@benthamscience.net

Gloria Badii

Neurofarba Department, University of Florence, Section of Pharmaceutical and Nutraceutical Sciences

Email: info@benthamscience.net

Fabrizio Carta

Neurofarba Department, University of Florence, Section of Pharmaceutical and Nutraceutical Sciences

Email: info@benthamscience.net

Cladiu T. Supuran

Neurofarba Department, University of Florence, Section of Pharmaceutical and Nutraceutical Sciences

Email: info@benthamscience.net

Nuray Ulusoy-Guzeldemirci

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University

Email: info@benthamscience.net

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