Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines

Abdelkhalek, Ahmed S.; Kothayer, Hend; Rezq, Samar; Orabi, Khaled Y.; Romero, Damián G.; El‐Sabbagh, Osama I.

doi:10.1016/j.ejmech.2023.115443

Cited by 5 publications

(1 citation statement)

References 49 publications

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“…[ 17 ] Accordingly, simultaneously inhibiting LOX‐mediated leukotriene synthesis and COX‐mediated prostaglandin synthesishas gained much attention as dual anti‐inflammatory targets. [ 18–20 ] Interestingly, NF‐κB plays an important role in the regulation of inflammatory and immune responses. Cytokines and chemokines encoding genes are regulated by NF‐κB promoting inflammation and inflammasome regulation.…”

Section: Introductionmentioning

confidence: 99%

Dual COX‐2 and 15‐LOX inhibition study of novel 4‐arylidine‐2‐mercapto‐1‐phenyl‐1H‐imidazolidin‐5(4H)‐ones: Design, synthesis, docking, and anti‐inflammatory activity

Osman,

Soltan,

Rezq

et al. 2024

Archiv der Pharmazie

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Novel arylidene‐5(4H)‐imidazolone derivatives 4a–r were designed and evaluated as multidrug‐directed ligands, that is, inflammatory, proinflammatory mediators, and reactive oxygen species (ROS) inhibitors. All of the tested compounds showed cyclooxygenase (COX)‐1 inhibitory effect more than celecoxib and less than indomethacin and also demonstrated an improved inhibitory activity against 15‐lipoxygenase (15‐LOX). Compounds 4f, 4l, and 4p exhibited COX‐2 selectivity comparable to that of celecoxib, while 4k was the most selective COX‐2 inhibitor. Interestingly, the screened results showed that compound 4k exhibited a superior inhibition effect against 15‐LOX and was found to be the most selective COX‐2 inhibitor over celecoxib, whereas compound 4f showed promising COX‐2 and 15‐LOX inhibitory activities besides its inhibitory effect against ROS production and its lowering effect of both tumor necrosis factor‐α and interleukin‐6 levels by ∼80%. Moreover, compound 4f attenuated the lipopolysaccharide‐mediated increase in NF‐κB activation in RAW 264.7 macrophages. The preferred binding affinity of these molecules was confirmed by docking studies. We conclude that arylidene‐5(4H)‐imidazolone scaffolds provide promising hits for developing new synthons with anti‐inflammatory and antioxidant activities.

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Section: Introductionmentioning

confidence: 99%

Dual COX‐2 and 15‐LOX inhibition study of novel 4‐arylidine‐2‐mercapto‐1‐phenyl‐1H‐imidazolidin‐5(4H)‐ones: Design, synthesis, docking, and anti‐inflammatory activity

Osman,

Soltan,

Rezq

et al. 2024

Archiv der Pharmazie

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Fused Thienopyrimidines as Versatile Pharmacophores for the Development of Cyclooxygenase‐2 Inhibitors

Thakur,

Arora,

Katiyar

et al. 2024

ChemistrySelect

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Inflammation is an essential body immune system response against various infections and tissue injuries and maintains normal homeostasis. Alterations in inflammatory responses lead to multiple disorders like heart diseases, obesity, diabetes, cancer, stroke, and neurodegenerative disorders. Cyclooxygenases (COXs), the enzymes, exist in two isoforms (COX‐1 and COX‐2) that catalyze the rate‐determining step of prostaglandin biogenesis and play a significant role in inflammation. COX‐2 inhibitors, although effective anti‐inflammatory agents are considered to be highly unsafe for long‐term usage due to their possible side and adversative effects. Recently, fused‐thienopyrimidines have emerged as a privileged scaffold with excellent anti‐inflammatory potential. In the present review, we have emphasized the recent developments in the design and synthetic strategies of fused‐thienopyrimidine derivatives and their detailed structure‐activity‐relationship (SAR) studies. The primary goal of this review is to provide restructuring knowledge about this template, which could prove beneficial and valuable for chemists working in the anti‐inflammatory area.

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Magic shotgun approach to anti-inflammatory pharmacotherapy: Synthesis of novel thienopyrimidine monomers/heterodimer as dual COX-2 and 15-LOX inhibitors endowed with potent antioxidant activity

Elsayed,

Abdelkhalek,

Rezq

et al. 2023

European Journal of Medicinal Chemistry

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Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines

Cited by 5 publications

References 49 publications

Dual COX‐2 and 15‐LOX inhibition study of novel 4‐arylidine‐2‐mercapto‐1‐phenyl‐1H‐imidazolidin‐5(4H)‐ones: Design, synthesis, docking, and anti‐inflammatory activity

Dual COX‐2 and 15‐LOX inhibition study of novel 4‐arylidine‐2‐mercapto‐1‐phenyl‐1H‐imidazolidin‐5(4H)‐ones: Design, synthesis, docking, and anti‐inflammatory activity

Fused Thienopyrimidines as Versatile Pharmacophores for the Development of Cyclooxygenase‐2 Inhibitors

Magic shotgun approach to anti-inflammatory pharmacotherapy: Synthesis of novel thienopyrimidine monomers/heterodimer as dual COX-2 and 15-LOX inhibitors endowed with potent antioxidant activity

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