2. Academic Validation
  3. Novel benzenesulfonamides aryl and arylsulfone conjugates adopting tail/dual tail approaches: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies

Novel benzenesulfonamides aryl and arylsulfone conjugates adopting tail/dual tail approaches: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies

  • Eur J Med Chem. 2021 Oct 5:221:113486. doi: 10.1016/j.ejmech.2021.113486.
Assem H Eldeeb 1,  Mahmoud F Abo-Ashour 2,  Andrea Angeli 3,  Alessandro Bonardi 4,  Deena S Lasheen 5,  Eman Z Elrazaz 5,  Alessio Nocentini 4,  Paola Gratteri 6,  Hatem A Abdel-Aziz 7,  Claudiu T Supuran 8
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, 11829, Egypt.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, 11829, Egypt. Electronic address: Mahmoud.Farid2020@gmail.com.
  • 3 Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.
  • 4 Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.
  • 5 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, P.O. Box 11566, Abbassia, Cairo, Egypt.
  • 6 Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.
  • 7 Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo, 12622, Egypt.
  • 8 Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.
PMID: 33965860 DOI: 10.1016/j.ejmech.2021.113486
Abstract

New series of benzenesulfonamide and benzoic acid derivatives were designed and synthesized using tail/dual tail approach to improve potency and selectivity as Carbonic Anhydrase inhibitors. The synthesized compounds evaluated as CAIs against isoforms hCA I, II, IV and IX with acetazolamide (AAZ) as standard inhibitor. The benzenesulfonamide derivatives 7a-d, 8a-h, 12a-c, 13a and 15a-c showed moderate to potent inhibitory activity with selectivity toward isoform hCA II, especially, compound 13a with (Ki = 7.6 nM), while the benzoic acid analogues 12d-f, 13b and 15d-f didn't show any activity except compounds 12d,f and 15e that showed weak activity. Additionally, molecular docking was performed for compounds 7a, 8a, 8e, 12a, 13a and 15a on isoform hCA I, II to illustrate the possible interaction with the active site to justify the inhibitory activity.

Keywords

Benzenesulfonamides; Carbonic anhydrase inhibitors; Dual tail approaches; Molecular docking; Synthesis; Tail approaches.

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