Abstract

Abstract

Multiple inhibitions of CA, COX-2 and 5-LOX enzymes has been recognised as a useful strategy for the development of anti-inflammatory drugs that can avoid the disadvantages of using NSAIDs alone. Here, we report new pyridazine-based sulphonamides (5a-c and 7a-f) as potential multi-target anti-inflammatory candidates. First, the furanone heterocycle in the dual CA/COX-2 inhibitor Polmacoxib was replaced with the pyridazinone one. Then, a hydrophobic tail was appended through benzylation of the 3-hydroxyl group of the pyridazinone scaffold to afford benzyloxy pyridazines 5a-c. Furthermore, the structures were adorned with the polar sulphonate functionality, in pyridazine sulphonates 7a-f, that are expected to be engaged in interactions with the hydrophilic half of the CA binding sites. All of the disclosed pyridazinones were tested for inhibitory activities against 4 hCA isoforms (I, II, IX, and XII), as well as against COX-1/2, and 5-LOX. Furthermore, in vivo anti-inflammatory and analgesic effects of pyridazinones 7a and 7b were examined.

Details

Title
Identification of new 4-(6-oxopyridazin-1-yl)benzenesulfonamides as multi-target anti-inflammatory agents targeting carbonic anhydrase, COX-2 and 5-LOX enzymes: synthesis, biological evaluations and modelling insights
Author
Badawi, Waleed A 1 ; Rashed, Mahmoud 2 ; Nocentini, Alessio 3 ; Bonardi, Alessandro 3 ; Abd-Alhaseeb, Mohammad M 4 ; Al-Rashood, Sara T 5 ; Giri Babu Veerakanellore 6 ; Majrashi, Taghreed A 7 ; Elkaeed, Eslam B 8 ; Elgendy, Bahaa 9 ; Gratteri, Paola 10 ; Supuran, Claudiu T 11 ; Eldehna, Wagdy M 12 ; Elagawany, Mohamed 1 

1  Department of Pharmaceutical Chemistry, Damanhour University , Damanhour , Buhaira , Egypt 
2  Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy, Al-Azhar University , Cairo , Egypt 
3  Department of Neurofarba, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence , Firenze , Sesto Fiorentino , Italy, Department of Neurofarba, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico , Firenze , Sesto Fiorentino , Italy 
4  Department of Pharmacology and Toxicology, Damanhour University , Damanhour , Buhaira , Egypt 
5  Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University , Riyadh , Saudi Arabia 
6  Center for Clinical Pharmacology, Washington University School of Medicine and University of Health Sciences and Pharmacy , St. Louis , MO , USA 
7  Department of Pharmacognosy, College of Pharmacy, King Khalid University , Abha , Saudi Arabia 
8  Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University , Riyadh , Saudi Arabia 
9  Center for Clinical Pharmacology, Washington University School of Medicine and University of Health Sciences and Pharmacy , St. Louis , MO , USA, Chemistry Department, Faculty of Science, Benha University , Benha , Egypt 
10  Department of Neurofarba, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence , Firenze , Sesto Fiorentino , Italy 
11  Department of Neurofarba, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico , Firenze , Sesto Fiorentino , Italy 
12  Department of Pharmaceutical Chemistry, Kafrelsheikh University , Kafrelsheikh , Egypt 
Publication year
2023
Publication date
Dec 2023
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/14756366.2023.2201407
ProQuest document ID
2917549060
Copyright
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.