Design, synthesis and biological evaluation of novel pyrazole sulfonamide derivatives as dual COX-2/5-LOX inhibitors

Gedawy, Ehab M.; Kassab, Asmaa E.; Kerdawy, Ahmed M. El

doi:10.1016/j.ejmech.2020.112066

Cited by 65 publications

(36 citation statements)

References 51 publications

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“…Furthermore, docking studies of the most active compound showed that the acetate moiety of 20a was involved in a Hbonding interaction with the Tyr385 of the COX-2 enzyme. In addition, the 1-phenyl substituent attached to the core pyrazolo [4,3- Pyrazole sulfonamide conjugates 21 were prepared and evaluated for their in vitro analgesic and dual COX-2/5-LOX inhibitory activity [74]. The pyrazole derivative with a benzothiophene (conmpound 21a) exhibited potent inhibitory activity with the IC 50 values of 5.40 µM (COX-1), 0.014 µM (COX-2) and 1.78 µM (5-LOX) ( Figure 25).…”

Section: Pyrazolesmentioning

confidence: 99%

“…Anti-inflammatory activity of the most active pyrazole fused triazole hybrid 20a.Pyrazole sulfonamide conjugates 21 were prepared and evaluated for their in vitro analgesic and dual COX-2/5-LOX inhibitory activity[74]. The pyrazole derivative with a benzothiophene (conmpound 21a) exhibited potent inhibitory activity with the IC50 values of 5.40 M (COX-1), 0.014 M (COX-2) and 1.78 M (5-LOX)(Figure 25).…”

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confidence: 99%

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A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

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Section: Pyrazolesmentioning

confidence: 99%

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confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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“…Dual COX-2/5-LOX inhibitors had demonstrated excellent analgesic and anti-inflammatory activities with lower gastric irritation, bleeding and ulcerogenic side effects, and are an interesting alternative to provide safer NSAIDs 30 , 37 , 43 , 97 – 99 . The development of drugs with dual inhibitory activity for COX-2/5-LOX enzymatic pathways offers new options for the development of more effective anti-inflammatory agents with an improved safety profile.…”

Section: Resultsmentioning

confidence: 99%

“…In π-π T-shaped interaction π-electron cloud between the aromatic groups of amino acid fragments and non-chlorinated aromatic ring on diclofenac in a T-shaped manner, i.e., sidewise electron cloud of the ring and head on electron cloud of other ring, these bonds/interactions are necessary to have temporary interactions, especially for the drug action to be accomplished in a system, in addition interactions involving aromatic rings are major contributors to protein-ligand recognition and concomitantly to drug design. Dual COX-2/5-LOX inhibitors had demonstrated excellent analgesic and anti-inflammatory activities with lower gastric irritation, bleeding and ulcerogenic side effects, and are an interesting alternative to provide safer NSAIDs 30,37,43,[97][98][99] . The development of drugs with dual inhibitory activity for COX-2/5-LOX enzymatic pathways offers new options for the development of more effective anti-inflammatory agents with an improved safety profile.…”

Section: Evaluation Of the Docking Of Cox With Eugenol And Nsaids (Dimentioning

confidence: 99%

Computational analysis of eugenol inhibitory activity in lipoxygenase and cyclooxygenase pathways

Andrade

Mendes

2020

Sci Rep

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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.

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“…COX-1 and COX-2 catalyze the biosynthesis of prostaglandins, prostacyclins, 4 Oxidative Medicine and Cellular Longevity and thromboxanes [68]. COX-1 and COX-2 share a very high degree of sequence identity and very similar active site topologies [75].…”

Section: Nuclear Factor Erythroid 2-related Factor 2 (Nrf2)mentioning

confidence: 99%

Identification of New Targets and the Virtual Screening of Lignans against Alzheimer’s Disease

Maia

Rodrigues

Sousa

et al. 2020

Oxidative Medicine and Cellular Longevity

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Alzheimer’s disease (AD) is characterized by the progressive disturbance in cognition and affects approximately 36 million people, worldwide. However, the drugs used to treat this disease are only moderately effective and do not alter the course of the neurodegenerative process. This is because the pathogenesis of AD is mainly associated with oxidative stress, and current drugs only target two enzymes involved in neurotransmission. Therefore, the present study sought to identify potential multitarget compounds for enzymes that are directly or indirectly involved in the oxidative pathway, with minimal side effects, for AD treatment. A set of 159 lignans were submitted to studies of QSAR and molecular docking. A combined analysis was performed, based on ligand and structure, followed by the prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. The results showed that the combined analysis was able to select 139 potentially active and multitarget lignans targeting two or more enzymes, among them are c-Jun N-terminal kinase 3 (JNK-3), protein tyrosine phosphatase 1B (PTP1B), nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NADPH quinone oxidoreductase 1 (NQO1), phosphodiesterase 5 (PDE5), nuclear factor erythroid 2-related factor 2 (Nrf2), cycloxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). The authors conclude that compounds (06) austrobailignan 6, (11) anolignan c, (19) 7-epi-virolin, (64) 6-[(2R,3R,4R,5R)-3,4-dimethyl-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]-4-methoxy-1,3-benzodioxole, (116) ococymosin, and (135) mappiodoinin b have probabilities that confer neuroprotection and antioxidant activity and represent potential alternative AD treatment drugs or prototypes for the development of new drugs with anti-AD properties.

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Design, synthesis and biological evaluation of novel pyrazole sulfonamide derivatives as dual COX-2/5-LOX inhibitors

Cited by 65 publications

References 51 publications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

Computational analysis of eugenol inhibitory activity in lipoxygenase and cyclooxygenase pathways

Identification of New Targets and the Virtual Screening of Lignans against Alzheimer’s Disease

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