Design and synthesis of pyridazinone hybrid in PEG-400 as COX-1/COX-2 inhibitor and their antioxidant study

Abstract The cyclooxygenase 1 and 2 (COX-1 and COX-2) are the key enzymes that are responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as a double-edged weapon to inhibit COX-1 can lead to gastrointestinal side...

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Main Authors: Omprakash B. Pawar, Anil P. Marale, Deekshaputra R. Birhade, Rahul D. Jawarkar, Avinash G. Ulhe, Gajanan D. Rawate, Nagesh R. Nahate, Shashikant A. Ikhe, Dinesh A. Pund, Gajanan N. Chaudhari, Vivek T. Humne
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Chemistry
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Online Access:https://doi.org/10.1007/s44371-025-00216-w
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Summary:Abstract The cyclooxygenase 1 and 2 (COX-1 and COX-2) are the key enzymes that are responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as a double-edged weapon to inhibit COX-1 can lead to gastrointestinal side effects and kidney damage, whereas selective COX-2 inhibition provides anti-inflammatory effects without gastrointestinal toxicity. In this report, we described the modular synthesis of substituted pyridazin-3(2H)-ones in polyethylene glycol-400, as a green solvent. The products were isolated without the use of column chromatography, which makes this process elegant and efficient. The compounds 2e and 2 l show the top-tier selective index for cyclooxygenase, in comparable with celecoxib as a standard. Besides, the antioxidant activity of the synthesized compounds has also been tested. The binding mode of 2 h was evaluated through in silico molecular docking, while ADME assessment studies predicted the drug-like characteristics of the synthesised compounds (2a-p). The newly developed protocol and synthesized compounds may serve as a structural guide for designing and development of cyclooxygenase inhibitors. Graphical abstract
ISSN:3005-1193