A novel class of tyrosine derivatives as dual 5-LOX and COX-2/mPGES1 inhibitors with PGE<sub>2</sub> mediated anticancer properties

Puratchikody, Ayarivan; Umamaheswari, A; Irfan, Navabshan; Sinha, Sanjib; Manju, S. L.; Ramanan, Meera; Ramamoorthy, Gayathri; Doble, Mukesh

doi:10.1039/c8nj04385j

Cited by 15 publications

(4 citation statements)

References 39 publications

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“…LOXs catalyze the transformation of arachidonic acid into three types of hydroxyeicosatetraenoic acids (HETEs)-5-HPETE or 5-HETE by 5-LOX, 12-HETEs by 12-LOX and 15-HETEs by 15-LOX. 5-HETE is the precursor of leukotriene LTA 4 , which is converted into lipid mediators LTB 4, LTC 4, LTD 4, LTE 4 that induce asthma and inflammation [196,197]. Studies have found that 5-HETE and 5-HPETE stimulate the generation of superoxide in human neutrophils, and trigger the ROS stress [198].…”

Section: Arachidonic Acid Metabolism Pathway and Inflammationmentioning

confidence: 99%

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Sodji

Oyelere

2022

Cancers

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Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chronic inflammatory diseases and cancers. We also recognized the value of the re-evaluation of the disease-specific roles of multiple pathways implicated in the pathophysiology of chronic inflammatory diseases and cancers—as well as the application of data from single-cell RNA sequencing in the success of future drug discovery endeavors.

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Section: Arachidonic Acid Metabolism Pathway and Inflammationmentioning

confidence: 99%

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Sodji

Oyelere

2022

Cancers

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“…When IL-1 β binds to its receptor, the activity of COX-2 is increased. COX-2 has a catalytic role in the conversion of arachidonic acid to PGE and PGE2 under the action of PGE synthetase [ 22 ]. PGE2 can increase vascular permeability and dilate blood vessels, resulting in bronchial mucosal edema, increased gland secretion, and airway obstruction by exudates [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Reineckia carnea Alleviates the Production of Inflammatory Cytokines and MUC5AC in Rats with Chronic Obstructive Pulmonary Disease

Liu

Li³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Reineckia carnea (RC), a perennial evergreen herb which belongs to Reineckia Kunth (Liliaceae), can be used for clearing the lungs and relieving cough, reducing phlegm and anti-inflammatory effects. Moreover, chronic obstructive pulmonary disease (COPD) is characterized by airway and lung inflammation and increased secretion of airway mucus. Therefore, RC has the potential to treat COPD. Methods. NR8383 cells were cultured and treated with various concentrations of RC (100 mg/mL, 10 mg/mL, 1 mg/mL, 100 μg/mL, 10 μg/mL, 1 μg/mL, 100 ng/mL, and 10 ng/mL). Cell viability and levels of interleukin (IL)-1β, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the cell culture supernatant or rat serum were analyzed using CCK-8 and enzyme-linked immunosorbent assay (ELISA), respectively. Sprague Dawley rats were assigned to mock, COPD model, RC (0.67 g/kg, 1.35 g/kg, and 2.7 g/kg), and ambroxol (5.4 mg/kg) groups. Western blot and quantitative polymerase chain reaction (qPCR) analyses were used to evaluate the protein and mRNA expression levels of mucin 5AC (MUC5AC) and Toll-like receptor 4 (TLR4). Results. The results showed that Reineckia carnea (RC) extract (RCE) inhibited the proliferation of NR8383 cells and suppressed the production of IL-1β, PGE2, and COX-2 in NR8383 cells. Moreover, RCE decreased the levels of IL-1β, PGE2, and COX-2 in the serum of rats with COPD and alleviated the expression of TLR4 and MUC5AC induced by COPD in rat lung tissue. Conclusion. RCE alleviated COPD by inhibiting the expression of COPD-induced inflammatory cytokines and MUC5AC in rats.

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“…Puratchikody et al 187 synthesized a series of novel tyrosine derivatives to favor the inhibition of 5-LOX and PGE 2 production. Most of the synthesized derivatives could be further optimized and developed as drugs against inflammation and cancer.…”

Section: Recently Reported Cox Inhibitorsmentioning

confidence: 99%

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective

et al. 2023

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Innate inflammation beyond a threshold is a significant problem involved in cardiovascular diseases, cancer, and many other chronic conditions. Cyclooxygenase (COX) enzymes are key inflammatory markers as they catalyze prostaglandins production and are crucial for inflammation processes. While COX-I is constitutively expressed and is generally involved in "housekeeping" roles, the expression of the COX-II isoform is induced by the stimulation of different inflammatory cytokines and also promotes the further generation of pro-inflammatory cytokines and chemokines, which affect the prognosis of various diseases. Hence, COX-II is considered an important therapeutic target for drug development against inflammation-related illnesses. Several selective COX-II inhibitors with safe gastric safety profiles features that do not cause gastrointestinal complications associated with classic antiinflammatory drugs have been developed. Nevertheless, there is mounting evidence of cardiovascular side effects from COX-II inhibitors that resulted in the withdrawal of market-approved anti-COX-II drugs. This necessitates the development of COX-II inhibitors that not only exhibit inhibit potency but also are free of side effects. Probing the scaffold diversity of known inhibitors is vital to achieving this goal. A systematic review and discussion on the scaffold diversity of COX inhibitors are still limited. To address this gap, herein we present an overview of chemical structures and inhibitory activity of different scaffolds of known COX-II inhibitors. The insights from this article could be helpful in seeding the development of next-generation COX-II inhibitors.

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A novel class of tyrosine derivatives as dual 5-LOX and COX-2/mPGES1 inhibitors with PGE₂ mediated anticancer properties

Abstract: Leukotriene and prostaglandin pathways are controlled by the enzymes, LOX and COX/mPGES1 respectively and are responsible for inflammatory responses.

Cited by 15 publications

References 39 publications

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Reineckia carnea Alleviates the Production of Inflammatory Cytokines and MUC5AC in Rats with Chronic Obstructive Pulmonary Disease

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective

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A novel class of tyrosine derivatives as dual 5-LOX and COX-2/mPGES1 inhibitors with PGE2 mediated anticancer properties

Abstract: Leukotriene and prostaglandin pathways are controlled by the enzymes, LOX and COX/mPGES1 respectively and are responsible for inflammatory responses.

Cited by 15 publications

References 39 publications

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Reineckia carnea Alleviates the Production of Inflammatory Cytokines and MUC5AC in Rats with Chronic Obstructive Pulmonary Disease

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective

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Resources

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A novel class of tyrosine derivatives as dual 5-LOX and COX-2/mPGES1 inhibitors with PGE₂ mediated anticancer properties