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Challenging inflammatory process at molecular, cellular and in vivo levels via some new pyrazolyl thiazolones.

PMID: 33618602 (view PubMed database entry)
DOI: 10.1080/14756366.2021.1887169 (read at publisher's website )
PMCID: PMC7901699 (free full text version available)

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Perihan A Elzahhar, Rana A Alaaeddine, Rasha Nassra, Azza Ismail, Hala F Labib, Mohamed G Temraz, Ahmed S F Belal, Ahmed F El-Yazbi,

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 (IC<sub>50</sub> values of 0.09-0.14 µM) with significant 15-LOX inhibitory activities (IC<sub>50</sub>s 1.96 to 3.52 µM). Upon investigation of their <i>in vivo</i> 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, <i>in silico</i> predictions confirmed the appropriateness of these compounds as drug-like candidates.

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2021, 36(1):669-684]

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