Enhancement of the Anti-Inflammatory Activity of NSAIDs by Their Conjugation with 3,4,5-Trimethoxybenzyl Alcohol

Tziona, Paraskevi; Theodosis-Nobelos, Panagiotis; Papagiouvannis, Georgios; Petrou, Anthi; Drouza, Chryssoula; Rekka, Eleni A.

doi:10.3390/molecules27072104

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…injection of 0.1 mL of an aqueous carrageenan solution (1% w / v ) in the hind paw of rats. The produced oedema, after 3.5 h, was estimated as paw weight increase [ 44 ].…”

Section: Methodsmentioning

confidence: 99%

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study

2022

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Alzheimer’s Disease (AD) is a common neurodegenerative disorder characterized by memory loss and cognitive impairment. Its pathology has not been fully clarified and therefore highly effective treatments have not been obtained yet. Almost all the current treatment options aim to alleviate only the symptoms and not to eliminate the disease itself. Acetylcholinesterase inhibitors are the main therapeutic agents against AD, whereas oxidative stress and inflammation have been found to be of great significance for the development and progression of neurodegeneration. In this work, ethyl nipecotate (ethyl-piperidine-3-carboxylate), a heterocyclic carboxylic acid derivative, which acts as a GABA reuptake inhibitor and has been used in research for diseases involving GABAergic neurotransmission dysfunction, was amidated with various carboxylic acids bearing antioxidant and/or anti-inflammatory properties (e.g., ferulic acid, sinapic acid, butylated hydroxycinnamic acid). Most of our compounds have significant antioxidant potency as lipid peroxidation inhibitors (IC50 as low as 20 μΜ), as oxidative protein glycation inhibitors (inhibition up to 57%), and act as DPPH reducing agents. Moreover, our compounds are moderate LOX inhibitors (up to 33% at 100 μΜ) and could reduce rat paw edema induced by carrageenan by up to 61%. Finally, some of them possessed inhibitory activity against acetylcholinesterase (IC50 as low as to 47 μΜ). Our results indicate that our compounds could have the potentiality for further optimization as multi-targeting agents directed against AD.

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“…injection of 0.1 mL of an aqueous carrageenan solution (1% w / v ) in the hind paw of rats. The produced oedema, after 3.5 h, was estimated as paw weight increase [ 44 ].…”

Section: Methodsmentioning

confidence: 99%

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study

2022

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“…X-ray crystal structures of COX-1 (PDB code: 1EQG) [ 71 ], COX-2 (PDB code: 1CX2) [ 72 ], LOX (PDB code: 6N2W) with their corresponding bound inhibitors, were retrieved from Protein Data Bank (PDB). All procedures were carried out following our previously reported work [ 73 ].…”

Section: Methodsmentioning

confidence: 99%

Discovery of 5-Methylthiazole-Thiazolidinone Conjugates as Potential Anti-Inflammatory Agents: Molecular Target Identification and In Silico Studies

et al. 2022

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A series of previously synthesized 5-benzyliden-2-(5-methylthiazole-2-ylimino)thiazoli- din-4-one were evaluated for their anti-inflammatory activity on the basis of PASS predictive outcomes. The predictive compounds were found to demonstrate moderate to good anti-inflammatory activity, and some of them displayed better activity than indomethacin used as the reference drug. Structure–activity relationships revealed that the activity of compounds depends not only on the nature of the substituent but also on its position in the benzene ring. The most active compounds were selected to investigate their possible mechanism of action. COX and LOX activity were determined and found that the title compounds were active only to COX-1 enzymes with an inhibitory effect superior to the reference drug naproxen. As for LOX inhibitory activity, the derivatives failed to show remarkable LOX inhibition. Therefore, COX-1 has been identified as the main molecular target for the anti-inflammatory activity of our compounds. The docking study against COX-1 active site revealed that the residue Arg 120 was found to be responsible for activity. In summary, the 5-thiazol-based thiazolidinone derivatives have been identified as a novel class of selective COX-1 inhibitors.

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“…After 3.5 h, the hind paws were excised and were weighed separately. The edema paws were estimated as paw weight increase [48].…”

Section: Effect On Mouse Paw Edema In Carrageenan-inducedmentioning

confidence: 99%

“…The assay analyzes PGF 2a produced by SnCl 2 reduction of COX-derived PGH 2 . The prostanoid product was quantified using enzyme immunoassay via a broadly specific antibody that binds to all major prostaglandin compounds [48].…”

Section: Cox-1 and Cox-2 Activity Inhibitionmentioning

confidence: 99%

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Identification of Novel Cyclooxygenase-1 Selective Inhibitors of Thiadiazole-Based Scaffold as Potent Anti-Inflammatory Agents with Safety Gastric and Cytotoxic Profile

et al. 2023

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Major obstacles faced by the use of nonsteroidal anti-inflammatory drugs (NSAID) are their gastrointestinal toxicity induced by non-selective inhibition of both cyclooxygenases (COX) 1 and 2 and their cardiotoxicity associated with a certain class of COX-2 selective inhibitors. Recent studies have demonstrated that selective COX-1 and COX-2 inhibition generates compounds with no gastric damage. The aim of the current study is to develop novel anti-inflammatory agents with a better gastric profile. In our previous paper, we investigated the anti-inflammatory activity of 4-methylthiazole-based thiazolidinones. Thus, based on these observations, herein we report the evaluation of anti-inflammatory activity, drug action, ulcerogenicity and cytotoxicity of a series of 5-adamantylthiadiazole-based thiazolidinone derivatives. The in vivo anti-inflammatory activity revealed that the compounds possessed moderate to excellent anti-inflammatory activity. Four compounds 3, 4, 10 and 11 showed highest potency (62.0, 66.7, 55.8 and 60.0%, respectively), which was higher than the control drug indomethacin (47.0%). To determine their possible mode of action, the enzymatic assay was conducted against COX-1, COX-2 and LOX. The biological results demonstrated that these compounds are effective COX-1 inhibitors. Thus, the IC50 values of the three most active compounds 3, 4 and 14 as COX-1 inhibitors were 1.08, 1.12 and 9.62 μΜ, respectively, compared to ibuprofen (12.7 μΜ) and naproxen (40.10 μΜ) used as control drugs. Moreover, the ulcerogenic effect of the best compounds 3, 4 and 14 were evaluated and revealed that no gastric damage was observed. Furthermore, compounds were found to be nontoxic. A molecular modeling study provided molecular insight to rationalize the COX selectivity. In summary, we discovered a novel class of selective COX-1 inhibitors that could be effectively used as potential anti-inflammatory agents.

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Enhancement of the Anti-Inflammatory Activity of NSAIDs by Their Conjugation with 3,4,5-Trimethoxybenzyl Alcohol

Cited by 9 publications

References 33 publications

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study

Discovery of 5-Methylthiazole-Thiazolidinone Conjugates as Potential Anti-Inflammatory Agents: Molecular Target Identification and In Silico Studies

Identification of Novel Cyclooxygenase-1 Selective Inhibitors of Thiadiazole-Based Scaffold as Potent Anti-Inflammatory Agents with Safety Gastric and Cytotoxic Profile

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