scholarly journals Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

2019 ◽  
Vol 28 (1) ◽  
pp. 138-146
Author(s):  
Mustafa H. Ali Alsafi ◽  
Muthanna S. Farhan
Keyword(s):  
Side Effects ◽  
Mefenamic Acid ◽  
Paw Edema ◽  
Compound I ◽  
Reference Drug ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Derivatives Of ◽  
Cox 1 ◽  
Inflammatory Effect

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect.

scholarly journals Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

2019 ◽  
Vol 28 (1) ◽  
pp. 140-148
Author(s):  
Mustafa Hussein Al ◽  
Muthanna S. Farhan
Keyword(s):  
Side Effects ◽  
Mefenamic Acid ◽  
Control Group ◽  
Compound I ◽  
Gastric Bleeding ◽  
Potent Effect ◽  
Reference Drug ◽  
Anti Inflammatory ◽  
Derivatives Of ◽  
Inflammatory Effect

Mefenamic acid (MA) widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to produce compound (II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white (i.p) induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.). On the other hand compound IVc exhibited lower anti-inflammatory effect.

scholarly journals The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3701
Author(s):  
Salah E. M. Eltom ◽  
Ahmed A. H. Abdellatif ◽  
Hamzah Maswadeh ◽  
Mohsen S. Al-Omar ◽  
Atef A. Abdel-Hafez ◽  
...  
Keyword(s):  
Oral Administration ◽  
Standard Procedure ◽  
P Value ◽  
Skin Thickness ◽  
Paw Edema ◽  
Reference Drug ◽  
Struthio Camelus ◽  
Anti Inflammatory ◽  
Nano Emulsion ◽  
Inflammatory Effect

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

scholarly journals Synthesis of Novel Diclofenac Hydrazones: Molecular Docking, Anti-Inflammatory, Analgesic, and Ulcerogenic Activity

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Nawaf A. Alsaif ◽  
Mashooq A. Bhat ◽  
Mohamed A. Al-Omar ◽  
Hanaa M. Al-Tuwajiri ◽  
Ahmed M. Naglah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Analgesic Activity ◽  
Binding Affinities ◽  
Standard Drug ◽  
Reference Drug ◽  
Ulcerogenic Activity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Sparing Effect ◽  
Cox 1

This study was aimed to design novel diclofenac hydrazones having anti-inflammatory and analgesic activity with gastric sparing effect. A new series of 2-[2-(2,6-dichloroanilino)phenyl]-N’-[(substituted phenyl) methylidene] acetohydrazide derivatives (1−14) were synthesized and evaluated for their anti-inflammatory, analgesic, and ulcerogenic activity. The compounds were identified and confirmed by elemental analysis and spectral data. During anti-inflammatory activity by carrageenan-induced paw edema method, compounds (2, 3, 7, 8, 11, and 13) were found to be most promising. Compounds 3, 8, and 13 have been found to have significant analgesic activity compared to the reference drug diclofenac in analgesic activity by both the hot plate method and acetic acid-induced writhing method. The compounds which presented highly significant anti-inflammatory and analgesic activity were further tested for their ulcerogenic activity. Compounds 3 and 8 showed maximum ulcerogenic reduction activities. Compound 8 was found to have LD50 of 168 mg/kg. Compound 8 with 3,5-dimethoxy-4-hydroxyphenyl substitution was found to be the most promising anti-inflammatory and analgesic agent with gastric sparing activity. Molecular docking of compounds was performed for COX−1/COX−2 binding site. Lead compound 8 showed better binding affinities of −9.4 kJ/mol with both COX-1 and COX-2 as compared to the standard drug, diclofenac with binding affinities of −6.6 kJ/mol and −8.1 kJ/mol for COX−1 and COX−2, respectively.

scholarly journals Synthesis, Molecular Modelling and Biological Evaluation of Novel Pyrimidine Derivatives as Anti-inflammatory Agents

2020 ◽  
pp. 49-67
Author(s):  
Naglaa Mohamed Ahmed ◽  
Shahira Nofal ◽  
Samir Mohamed Awad
Keyword(s):  
Docking Studies ◽  
Biological Evaluation ◽  
Inflammatory Activity ◽  
Pyrimidine Derivatives ◽  
Reference Drug ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1 ◽  
Good Agreement

Aim: As part of ongoing studies in developing new anti-inflammatory agents, 2-thioxo-1,2,3,4-tetrahydropyrimidine derivative 1 was synthesized by direct Biginelli condensation and used for the synthesis of novel series of  pyrimidin-2-thione derivatives  (2a-d to 7a-b). Materials and Methods: All compounds were examined for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay in comparison to ibuprofen, as a reference drug. Molecular docking studies were carried out using SYBLYL-X v.2.1 software. Study Design: A series of pyrimidine derivatives were synthesized by a simple and available method leads to a molecule of promising anti-inflammatory activity, the docking studies show good agreement with anti-inflammatory results. Future researches are recommended to assure the importance of these new derivatives for various applications. Place and Duration of Study: Pharmaceutical Organic Chemistry Department and Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt, between February 2018 and March 2019. Results: Compounds showed 61 to 86% anti-inflammatory activity where-as ibuprofen showed 69% activity. Compounds 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d, 7a, 7b induced strong anti-inflammatory activity, comparable with that of ibuprofen, they showed significantly difference at 4h post-carrageenan. Compound 3c (86%) showed the best result of edema inhibition in rats. Moreover, compounds 1, 2c and 3c were subjected to in vitro enzyme assay investigations against COX-1 and COX-2. All tested compounds showed higher potency towards COX-2 over COX-1. Compound 3c realized higher potency towards COX-2 (IC50= 0.046 μM) than compounds 1(IC50= 0.21 μM) and 2c (IC50=0.11 μM) as well as ibuprofen (IC50= 43.628 μM). Structure-activity relationship (SAR) has been discussed. Conclusion: A series of pyrimidine derivatives were synthesized by a simple and available method gave a molecule of promising anti-inflammatory activity, the docking studies showed good agreement with anti-inflammatory results.

scholarly journals Antiinflammatory activity of 2-, 3-, 4-carboxymethylpyridinium hexafluorosilicates on carrageenan model of inflammation

2019 ◽  
pp. 82-87
Author(s):  
B. V. Pristupa ◽  
I. O. Shyshkin ◽  
Ya. V. Rozhkovsky ◽  
V. O. Gelmboldt
Keyword(s):  
Antiinflammatory Activity ◽  
Biologically Active ◽  
Inflammatory Activity ◽  
Male Rats ◽  
Control Group ◽  
Paw Edema ◽  
Commercial Preparation ◽  
Reference Drug ◽  
Anti Inflammatory ◽  
Inflammatory Effect

In the last decade, high cariesprophylactic efficacy of ammonium hexafluorosilicates, including salts with substituted biologically active ammonium cations, has been demonstrated. Among the promising anti-caries agents are recently synthesized 2-, 3-, 4-carboxymethylpyridinium hexafluorosilicates, for whose cations anti-inflammatory activity is expected. The aim of the work is to assess the presence of anti-inflammatory activity in the series of 2-, 3-, 4-carboxymethylpyridinium hexafluorosilicates in the experiment. 2-, 3-, 4-Carboxymethylpyridinium hexafluorosilicates (I–III, respectively) were synthesized according to the previously proposed technique, carrageenan is a commercial preparation, reference drug is a indomethacin. Experiments on the anti-inflammatory activity of hexafluorosilicates were performed on 77 white Wistar male rats weighing 174–190 g using the carrageenan model of inflammation. The inflammatory reaction was reproduced by subplantary administration of 0.1 ml of a 0.2% solution of carrageenan, the studied compounds were administered orally in doses 1/10, 1/20, 1/50 from LD50 for the compound III. It was established that after administration of carrageenan, animals of the control group showed marked paw edema, which gradually increased and was maximal after 24 hours of observation. According to the data obtained, the indices for compounds I-III practically do not differ from those of the control group. This indicates that, despite the results of the PASS forecast and the presence of acetic acid residue, an anti-inflammatory pharmacofor, in compounds I-III, the compounds under study do not have an anti-inflammatory effect in the carrageenan model. 2-, 3-, 4-Carboxymethylpyridinium hexafluorosilicates do not show the expected anti-inflammatory activity in the carrageenan model of inflammation.

scholarly journals Anti- inflammatory effect of Prunus tomentosa Thunb total flavones in LPS-induced RAW264.7 cells

2019 ◽  
Vol 17 (1) ◽  
pp. 685-693
Author(s):  
Chen Xi ◽  
Liu Yuanyuan ◽  
Zhao Dongshuang ◽  
Fan Ziwei ◽  
Cao Shuang ◽  
...  
Keyword(s):  
Significant Inhibition ◽  
Raw264.7 Cells ◽  
Supernatant Fraction ◽  
Treatment Of Diabetes ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Impact ◽  
Cox 1 ◽  
Inflammatory Effect

AbstractIn this research, we investigated possible anti-inflammatory roles of Prunus tomentosa Thunb Total Flavones (PTTTF) in LPS-induced RAW264.7 cells. PTTTF (4μg/ml and 40μg/ml) was applied to RAW264.7 cells induced with 1μg/ml LPS to test the impact of these flavones on neutrophil phagocytosis in vitro. Levels of prostaglandin E2 (PGE2) and two pro-inflammatory interleukin cytokines (i.e. IL-6 and IL-1β) in the supernatant fraction were tested via Enzyme-linked immunosorbent assays (ELISA). Expression of cyclooxygenases COX-1 and COX-2 was detected via RT-PCR. Superoxide dismutase (SOD) content was determined with a spectrophotometric assay (Micromethod). The results revealed that PTTTF at doses higher than 4μg/ml reduces the content of IL-6, IL-1β and PGE2 (P < 0.05), and elevates the activity of SOD in LPS-induced RAW264.7 cells significantly (P < 0.05). PTTTF at 40μg/ml showed no significant effect on the expression of COX-1(P>0.05) but resulted in a significant inhibition of COX-2 in LPS-induced RAW264.7 cells (P<0.05). In summary, PTTTF had a substantial potential anti-inflammatory effect through the alteration of the synthesis of some cytokines and other mediators of the process of inflammation. Novelty statement - Prunus tomentosa Thunb Total Flavones (PTTTF) have known roles in the treatment of diabetes, but here we show that they are also potential anti-inflammatory agents. Our results show that PTTTF exhibited anti-inflammatory effects through altering the synthesis of some cytokines and other mediators of the inflammatory process.

Mefenamic Acid Compared with Ibuprofen in the Treatment of Rheumatoid Arthritis

1977 ◽  
Vol 5 (3) ◽  
pp. 161-163 ◽  
Author(s):  
R D G Leslie
Keyword(s):  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Mefenamic Acid ◽  
Double Blind ◽  
Patient Study ◽  
Anti Inflammatory ◽  
Inflammatory Effect

A randomized double-blind within-patient study of mefenamic acid compared with ibuprofen was performed on forty patients with rheumatoid arthritis. It was concluded that mefenamic acid and ibuprofen had an analgesic and anti-inflammatory effect which was not significantly different in the dosages employed. Apart from six complaints of drowsiness on ibuprofen with two complaints on mefenamic acid, the side-effects were similar.

Cyclooxygenase isoforms and atherosclerosis

2003 ◽  
Vol 5 (9) ◽  
pp. 1-18 ◽  
Author(s):  
Orina Belton ◽  
Desmond J. Fitzgerald
Keyword(s):  
Side Effects ◽  
Chronic Administration ◽  
Selective Inhibition ◽  
Gastric Ulcers ◽  
Analgesic Effects ◽  
Vascular Regulation ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Effective Use ◽  
Cox 1

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain. However, their long-term use is limited by gastrointestinal (GI) side effects such as gastric ulcers. NSAIDs act by inhibiting an enzyme called cyclooxygenase. Cyclooxygenase (COX) catalyses the generation of prostaglandins from arachidonic acid. Two isoforms of the enzyme exist – COX-1 and COX-2 – both of which are targets for NSAIDs. Although they are associated with GI toxicity, NSAIDs have important antithrombotic and anti-inflammatory effects. The GI injury has been attributed to COX-1 inhibition and the anti-inflammatory effects to COX-2 inhibition. As COX-2 is traditionally viewed as an inducible enzyme, selective inhibition of COX-2 by ‘coxibs’ (selective COX-2 inhibitors) has been employed to achieve anti-inflammatory and analgesic effects without GI side effects. However, recently there have been suggestions that chronic administration of coxibs might increase the risk of cardiovascular events, such as atherosclerosis, compared with traditional NSAIDs. In vascular disease, there is increased expression of both COX-1 and COX-2, resulting in enhanced prostaglandin generation. The specific role of COX-1 and COX-2 in vascular regulation is still unknown but such knowledge is essential for the effective use of coxibs. Although more evidence is pointing to selective COX-1 inhibition as a therapeutic measure in inflammatory atherosclerosis, there are some studies that suggest that inhibition of COX-2 might have a potential benefit on atherosclerosis.

scholarly journals Synthesis, In Vivo Anti-Inflammatory Activity, and Molecular Docking Studies of New Isatin Derivatives

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ravi Jarapula ◽  
Kiran Gangarapu ◽  
Sarangapani Manda ◽  
Sriram Rekulapally
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Paw Edema ◽  
Molecular Docking Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

A novel synthesis of 2-hydroxy-N′-(2-oxoindolin-3-ylidene) benzohydrazide derivatives was synthesized by the condensation of 2-hydroxybenzohydrazide with substituted isatins. The synthesized compounds were characterized by FT-IR, 1H-NMR, and mass spectral data. Further, the compounds were screened for in vivo anti-inflammatory activity by carrageenan induced paw edema method. The tested compounds have shown mild-to-moderate anti-inflammatory activity. The compounds VIIc and VIId exhibited 65% and 63% of paw edema reduction, respectively. The molecular docking studies were also carried out into the active site of COX-1 and COX-2 enzymes (PDB ID: 3N8Y, 3LN1, resp.) using VLife MDS 4.3. The compounds VIIc, VIId, and VIIf exhibited good docking scores of −57.27, −62.02, and −58.18 onto the active site of COX-2 and least dock scores of −8.03, −9.17, and −8.94 on COX-1 enzymes and were comparable with standard COX-2 inhibitor celecoxib. A significant correlation was observed between the in silico and the in vivo studies. The anti-inflammatory and docking results highlight the fact that the synthesized compounds VIIc, VIId, and VIIf could be considered as possible hit as therapeutic agents.

scholarly journals In vitro Inhibitory Activities of Lauraceae Aporphine Alkaloids

2010 ◽  
Vol 5 (3) ◽  
pp. 1934578X1000500
Author(s):  
Ericsson David Coy Barrera ◽  
Luis Enrique Cuca Suárez
Keyword(s):  
Platelet Aggregation ◽  
Inhibitory Activities ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Lox Inhibitors ◽  
Cox 1 ◽  
Inflammatory Effect

The in vitro anti-inflammatory effect of eight aporphine alkaloids isolated from the leaves of two Lauraceae plants (Pleurothyrium cinereum and Ocotea macrophylla) was evaluated through inhibition of two isozymes of cyclooxygenase (COX-1 and COX-2), 5-lipoxygenase (5-LOX), and platelet aggregation induced by PAF, AA and ADP. All alkaloids exhibited inhibitory activities against COX-2 (IC50 25.9-116 μM range) and PAF- and AA-induced platelet aggregation, while only four and three of them were good COX-1 and 5-LOX inhibitors, respectively. (+)-N-acetyl-nornantenine 6 was the most potent COX-2, 5-LOX, AA and PAF inhibitor.

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