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   VIAFID ORCID Logo  ; Supuran, Claudiu T 11   VIAFID ORCID Logo  ; Eldehna, Wagdy M 12   VIAFID ORCID Logo  ; 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.