Computational analysis of eugenol inhibitory activity in lipoxygenase and cyclooxygenase pathways

Abstract

Chronic inflammation is triggered by numerous diseases such as osteoarthritis, Crohn's disease and cancer. The control of the pro-inflammatory process can prevent, mitigate and/or inhibit the evolution of these diseases. Therefore, anti-inflammatory drugs have been studied as possible compounds to act in these diseases. This paper proposes a computational analysis of eugenol in relation to aspirin and diclofenac and analyzing the ADMET profile and interactions with COX-2 and 5-LOX enzymes, important enzymes in the signaling pathway of pro-inflammatory processes. Through the analysis of ADMET in silico, it was found that the pharmacokinetic results of eugenol are similar to NSAIDs, such as diclofenac and aspirin. Bioinformatics analysis using coupling tests showed that eugenol can bind to COX-2 and 5-LOX. These results corroborate with different findings in the literature that demonstrate anti-inflammatory activity with less gastric irritation, bleeding and ulcerogenic side effects of eugenol. The results of bioinformatics reinforce studies that try to propose eugenol as an anti-inflammatory compound that can act in the COX-2/5-LOX pathways, replacing some NSAIDs in different diseases.

In Silico Evaluation of Iranian Medicinal Plant Phytoconstituents as Inhibitors against Main Protease and the Receptor-Binding Domain of SARS-CoV-2

“…In pi-alkyl interactions, a pi-electron cloud interacts with an aromatic group and the electron group of an alkyl group. In pi-sulfur interaction, the pi-electron cloud of an aromatic ring interacts with the lone pair of the electron cloud of the sulfur atom [ 59 ]. Pi-sigma interactions (pi-alkyl and pi-sulfur) are largely involved in charge transfer and help to intercalate drugs in the binding sites of receptors [ 60 ].…”

Biological Properties and Prospects for the Application of Eugenol—A Review

“…Evidence suggests that eugenol has the ability to inhibit the production of superoxide anions in neutrophils by inhibiting the Raf/MEK/ERK1/2/p47-phosphorylation pathway. It is also known to be an inhibitor of pro-inflammatory mediators, including IL-1β and IL-6, tumor necrosis factor alpha (TNF-α), prostaglandin E 2 (PGE 2 ), expression of inducible oxide nitrate synthase (iNOS) and expression of cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and leukotriene C4 and 5-lipoxygenase (5-LOX) [ 31 ]. Its anti-inflammatory activity is associated with preventing neutrophil/macrophage chemotaxis and inhibiting the synthesis of inflammatory neurotransmitters, such as prostaglandins and leukotrienes; in addition, eugenol dimers have shown chemopreventive properties by inhibiting cytokine expression in macrophages ( Figure 3 ) [ 4 , 32 ].…”

“…In silico bioinformatics studies by Das Chagas Pereira de Andrade and Mendes [ 31 ] found that eugenol may inhibit both COX-2 and 5-LOX. It is therefore possible that eugenol may act as an anti-inflammatory agent, thus allowing it to replace some NSAIDs (nonsteroidal anti-inflammatory drugs) in various diseases; it could also be used in the synthesis of new selective drugs to fight diseases associated with inflammatory processes, such as osteoarthritis or cancer.…”

“… The anticancer, anti-inflammatory, and antioxidant mechanism of action of eugenol (own elaboration based on [ 1 , 3 , 4 , 7 , 14 , 15 , 16 , 28 , 29 , 30 , 31 , 32 ]). …”

Chemical Characterization and Anti-Inflammatory Activity of Phytoconstituents from Swertia alata

“…So, this research acclaims its edge and novelty over other studies on the S. alata plant. A strong correlation between the potency of NSAID's as an inhibitor of prostaglandin synthesis and ulcerogenic activity has been observed [45,46]. Most potent compound SA-4 showed a severity index lower than the standard drug Indomethacin.…”