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Challenging inflammatory process at molecular, cellular and in vivo levels via some new pyrazolyl thiazolones
- Source :
- Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 669-684 (2021)
- Publication Year :
- 2021
- Publisher :
- Taylor & Francis Group, 2021.
-
Abstract
- The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC50 values of 0.09–0.14 µM) with significant 15-LOX inhibitory activities (IC50s 1.96 to 3.52 µM). Upon investigation of their in vivo anti-inflammatory activities and ulcerogenic profiles, these compounds showed activity patterns equivalent or more superior to diclofenac and/or celecoxib. Intriguingly, the most active compounds were more effective than diclofenac in suppressing monocyte-to-macrophage differentiation and inflammatory cytokine production by activated macrophages, as well as their ability to induce macrophage apoptosis. The latter finding potentially adds a new dimension to the previously reported anti-inflammatory mechanisms of similar compounds. These compounds were effectively docked into COX-2 and 15-LOX active sites. Also, in silico predictions confirmed the appropriateness of these compounds as drug-like candidates.
Details
- Language :
- English
- ISSN :
- 14756366 and 14756374
- Volume :
- 36
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8486ba12e33942d49a1c18389ba67e36
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/14756366.2021.1887169