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

Autor: Eldeeb AH; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, 11829, Egypt., Abo-Ashour MF; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, 11829, Egypt. Electronic address: Mahmoud.Farid2020@gmail.com., Angeli A; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy., Bonardi A; 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., Lasheen DS; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, P.O. Box 11566, Abbassia, Cairo, Egypt., Elrazaz EZ; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, P.O. Box 11566, Abbassia, Cairo, Egypt., Nocentini A; 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., Gratteri P; 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., Abdel-Aziz HA; Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo, 12622, Egypt., Supuran CT; 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.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2021 Oct 05; Vol. 221, pp. 113486. Date of Electronic Publication: 2021 Apr 27.
DOI: 10.1016/j.ejmech.2021.113486
Abstrakt: 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 (K i  = 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: