Synthesis of novel thiadiazole derivatives as selective COX-2 inhibitors

MedChemComm ◽  
2016 ◽  
Vol 7 (12) ◽  
pp. 2309-2327 ◽  
Author(s):  
Fatma A. Ragab ◽  
Helmi I. Heiba ◽  
Marwa G. El-Gazzar ◽  
Sahar M. Abou-Seri ◽  
Walaa A. El-Sabbagh ◽  
...  
Keyword(s):  
Paw Oedema ◽  
Analgesic Agents ◽  
Thiadiazole Derivatives ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Cox 2 Inhibitors ◽  
Rat Paw Oedema

A novel series of thiadiazole derivatives were designed and synthesized for evaluation as selective COX-2 inhibitors in vitro and were investigated in vivo as anti-inflammatory and analgesic agents against carrageenan-induced rat paw oedema model in irradiated rats.

scholarly journals Synthesis and Evaluation of New Coumarin Derivatives as Antioxidant, Antimicrobial, and Anti-Inflammatory Agents

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3251 ◽  
Author(s):  
Hanan M. Alshibl ◽  
Ebtehal S. Al-Abdullah ◽  
Mogedda E. Haiba ◽  
Hamad M. Alkahtani ◽  
Ghada E.A. Awad ◽  
...  
Keyword(s):  
Significant Inhibition ◽  
Coumarin Derivatives ◽  
Paw Oedema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Orally Active ◽  
Rat Paw Oedema ◽  
Sulfonamide Compound

New pyranocoumarin and coumarin-sulfonamide derivatives were prepared and evaluated for their antioxidant, antimicrobial, and/or anti-inflammatory activities. Coumarin-sulfonamide compounds 8a–d demonstrated significant antioxidant activity, while 7c,d, 8c,d, and 9c,d exhibited antimicrobial activity equal to or higher than the standard antimicrobials against at least one tested microorganism. Regarding the anti-inflammatory testing, pyranocoumarins 2b, 3a,b and 5c and coumarin-sulfonamide compound 9a showed more potent antiproteinase activity than aspirin in vitro; however, five compounds were as potent as aspirin. The anti-inflammatory activity of the promising compounds was further assessed pharmacologically on formaldehyde-induced rat paw oedema and showed significant inhibition of oedema. For in vitro COX-inhibitory activity of coumarin derivatives, pyranocoumarin derivative 5a was the most selective (SI = 152) and coumarin-sulfonamide derivative 8d was most active toward COX-2 isozyme. The most active derivatives met the in silico criteria for orally active drugs; thus, they may serve as promising candidates to develop more potent and highly efficient antioxidant, antimicrobial, and/or anti-inflammatory agents.

Synthesis of new ibuprofen hybrid conjugates as potential anti-inflammatory and analgesic agents

2020 ◽  
Vol 12 (15) ◽  
pp. 1369-1386
Author(s):  
Siva S Panda ◽  
Adel S Girgis ◽  
Hitesh H Honkanadavar ◽  
Riham F George ◽  
Aladdin M Srour
Keyword(s):  
Writhing Test ◽  
Rat Paw Edema ◽  
Analgesic Agents ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Inhibition Studies

Background: A new set of hybrid conjugates derived from 2-(4-isobutylphenyl)propanoic acid (ibuprofen) is synthesized to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. Results & methodology: Synthesized conjugates were screened for their anti-inflammatory, analgesic and ulcerogenic properties. Few conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test, while a fair number of conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate technique. The newly synthesized conjugates did not display any ulcerogenic liability. Conclusion: In vitro, COX-1 and COX-2 enzyme inhibition studies raveled compound 7e is more selective toward COX-2 compared with ibuprofen.

scholarly journals Anti-inflammatory properties of Dirinaria consimilis extracts in albino rats

2018 ◽  
Vol 4 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Vinay Bharadwaj Tatipamula ◽  
Girija Sastry Vedula
Keyword(s):  
Protein Denaturation ◽  
Chloroform Extract ◽  
Acetone Extract ◽  
Albino Rats ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Rat Paw Oedema

BackgroundEarlier, the lichens are used in traditional medicines by different cultures across the world. As the Dirinaria genus has been shown to be biologically active against inflammation in folklore, we assessed the in vitro and in vivo anti-inflammatory profile of Dirinaria consimilis.Material and methodsInitially, the hydroalcoholic extract of lichen, D. consimilis (Dc-HE) was prepared and re-extracted with n-hexane, chloroform, ethyl acetate, acetone and methanol. The resultant extracts were evaluated for their in vitro (protein denaturation method), acute toxicity and in vivo (formalin-induced rat paw oedema assay) anti-inflammatory studies.ResultsAmong all the tested extracts, the acetone and chloroform extract of D. consimilis depicted prominent anti-inflammatory activity in both the bioassays. The acetone extract inhibited protein denaturation with IC50 value of about 468 µg/mL while the standard (Indomethacin) with 120 µg/mL. Moreover, the Dc-HE was screened for acute toxicity studies in male albino rats up to 2000 mg/Kg b.w dosage. The in vivo anti-inflammatory analysis of acetone extract (200 mg/mL) showed potent reduction of rat paw oedema nearer to that of the standard, whereas chloroform extract depicted moderate depletion and the other extracts revealed mild inhibitory profile against inflammation.ConclusionThis study reveals that the lichen, D. consimilis might be a good source of anti-inflammatory agents.

Fibrinolytic, Anti-Inflammatory and Cytotoxic Potentialities of Extracts and Chemical Constituents of Manglicolous Lichen, Graphis ajarekarii Patw. & C. R. Kulk

2020 ◽  
Vol 10 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Vinay Bharadwaj Tatipamula ◽  
Girija Sastry Vedula
Keyword(s):  
Protein Denaturation ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Fibrin Clot ◽  
Hydroalcoholic Extract ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Rat Paw Oedema

Background: Lichens which are betide to mangroves are termed as Manglicolous Lichens (ML). As these ML are habituated under stress conditions, they are screened for unique metabolites and biological activities. Objective: The study aimed to establish the chemical and biological profile of ML, Graphis ajarekarii. Methods: The Ethyl Acetate Extract of G. ajarekarii (EAE) was subjected to chromatographic techniques and the obtained isolates were characterized by spectroscopic analysis. The hydroalcoholic extract of G. ajarekarii (AE), EAE, isolates and Hydroalcoholic Extract of host (HE) were evaluated for fibrinolytic (fibrin clot method), in vitro (protein denaturation method) and in vivo (formalin-induced rat paw oedema assay), anti-inflammatory and cytotoxicity (MTT assay) activities. Results: Chemical investigation of the EAE led to the isolation of two known compounds namely atranorin (1) and ribenone (2), which were confirmed by spectral data. The AE and EAE gradually lysed the fibrin clot with 94.54 and 65.07%, respectively, at 24 h. The AE inhibited protein denaturation of about 88.06%, while the standard (Indomethacin) with 93.62%. Similarly, the in vivo antiinflammatory analysis of AE (200 mg/mL) showed potent reduction of rat paw oedema than the standard, whereas EAE and 1 depicted moderate depletion. In addition, the AE revealed prominence inhibition on MCF-7, DU145 and K-562 with IC50 values of 69.5, 42.5 and 38 µg/mL, respectively, whereas the HE exhibited mild inhibitory profile against fibrin clot, inflammation and cancer. Conclusion: From the results, it can be concluded that the G. ajarekarii has an aptitude to act against coagulation, inflammation and cancer cells.

Anti-Inflammatory Constituents of Alchornea cordifolia Leaves

2015 ◽  
Vol 19 ◽  
pp. 60-64
Author(s):  
AA Ahmadu ◽  
A Agunu ◽  
EM Abdurrahman
Keyword(s):  
Medicinal Plant ◽  
West Africa ◽  
Ethyl Acetate ◽  
Leaf Extract ◽  
Methyl Gallate ◽  
Paw Oedema ◽  
Analgesic Agents ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Rat Paw Oedema

Alchornea cordifolia (Schum and Thonn) Muell. Arg. (Euphorbiaceae) is a traditional medicinal plant widely distributed in West Africa including Nigeria.The plant has been used for ethnomedicinal purposes against wounds, ulcers, and sores. The decoction of the leaves has been reported to provide remedies for bronchial problems, rheumatic pain and cough. From the dichloromethane and ethyl acetate soluble parts of the Methanol leaf extract, two compounds namely Lup-20(29)-en-3c-ol (lupenol) and Methyl 3, 4,5-trihydroxy benzoate (Methyl gallate) were isolated and their structures elucidated. Anti-inflammatory and analgesic properties of the compounds on carrageenan-induced paw oedema and formalin-induced pain in rats showed that compound 2 significantly (P<0.05) inhibit rat paw oedema compared to the standard drugs (Piroxicam and Morphine) used, while on formalin-induced pain in rats, the same trend was observed and were both comparable to Piroxicam and morphine, the standard anti-inflammatory and analgesic agents used, respectively. Compound 1 did not show any significant anti-inflammatory activity compared to control, likewise compound 2. Thus, compound 2, Methyl trihydroxy benzoate, might be responsible for the anti-inflammatory and analgesic properties of this plant.Keywords: Alchornea cordifolia, Anti-inflammatory, Analgesic, Methyl Trihydroxy Benzoate

scholarly journals Anti-Inflammatory Activity of Pleurotus ostreatus, a Culinary Medicinal Mushroom, in Wistar Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
W. J. A. Banukie N. Jayasuriya ◽  
Shiroma M. Handunnetti ◽  
Chandanie A. Wanigatunge ◽  
Gita H. Fernando ◽  
D. Thusitha U. Abeytunga ◽  
...  
Keyword(s):  
Pleurotus Ostreatus ◽  
Inflammatory Activity ◽  
No Production ◽  
Protective Effects ◽  
Paw Oedema ◽  
Freeze Dried ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Rat Paw Oedema

Context. Pleurotus ostreatus (P.o) is a culinary mushroom which is commonly called as “oyster mushroom” belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. Objectives. The present study investigates the anti-inflammatory potential of P.o and the underlying mechanisms of activity. Materials and Methods. Anti-inflammatory activity was evaluated using suspensions of freeze-dried and powdered (SFDP) P.o and acetone extract (AE) of P.o in normal and alloxan-induced diabetic rats using the carrageenan-induced rat paw oedema model. The mechanisms by which P.o is mediating the anti-inflammatory activity were studied using in vivo and in vitro assays. Results. At doses of 500–1000 mg/kg, the SFDP of P.o showed long-lasting activity at both early and late phases of carrageenan-induced rat paw oedema. The dose of 750 mg/kg showed the most potent inhibitory activity (92% inhibition) in healthy rats. The AE of P.o showed maximum inhibition of oedema of 87%. P.o exerted protective effects on the inflammatory pathologies in rats with diabetes. The possible mechanisms by which P.o mediates the anti-inflammatory activity were antihistamine activity (52.1%), inhibition of cell migration to the site of inflammation (45.4%), in vitro membrane stabilizing activity (52.6%), and inhibition of nitric oxide (NO) production (91.2%) (P<0.05). Dose-dependent inhibition of NO production was seen with in vitro treatment of rat peritoneal cells with AE of P.o (r = 0.95; P<0.05). Discussion and Conclusion. The promising activity of culinary mushroom P.o against inflammation suggests its potential application as a functional food during inflammatory conditions.

scholarly journals Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors

2007 ◽  
Vol 57 (1) ◽  
pp. 13-30 ◽  
Author(s):  
Mange Yadav ◽  
Shrikant Shirude ◽  
Devendra Puntambekar ◽  
Pinkal Patel ◽  
Hetal Prajapati ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

Studies in 3,4-diaryl-1,2,5-oxadiazoles and theirN-oxides: Search for better COX-2 inhibitorsA series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazoleN-oxides were prepared and evaluated for COX-2 and COX-1 binding affinityin vitroand for anti-inflammatory activity by the rat paw edema method.p-Methoxy (p-OMe) substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)-1,2,5-oxadiazoleN-oxide (42) showed COX-2 enzyme inhibition of 54% at 22 μmol L-1and COX-1 enzyme inhibition of 44% at 88 μmol L-1concentrations, but showed very lowin vivoanti-inflammatory activity. Its deoxygenated derivative (21) showed lower COX-2 enzyme inhibition (26% at 22 μmol L-1) and higher COX-1 enzyme inhibition (53% at 88 μmol L-1) but, markedin vivoanti-inflammatory activity (71% at 25 mg kg-1)vs.celecoxib (48% at 12.5 mg kg-1). Molecular modeling (docking) studies showed that the methoxy group is positioned in the vicinity of COX-2 secondary pocket and it also participates in hydrogen bonding interactions in the COX-2 active site. These preliminary studies suggest thatp-methoxy (p-OMe) group in one of benzene rings may give potentially active leads in this series of oxadiazole/N-oxides.

scholarly journals Synthesis, Characterization of Novel N'(2-Phenoxyacetyl)Nicotinohydrazide and N'(2-Phenoxyacetyl)Isonicotinohydrazide Derivatives as Anti-Inflammatory and Analgesic Agents

2021 ◽  
Author(s):  
H. M. Pallavi ◽  
Fares Hezam Al-Ostoot ◽  
Hamse Kameshwar Vivek ◽  
Shaukath Ara Khanum
Keyword(s):  
Acetic Acid ◽  
Three Dimensional ◽  
Thermal Pain ◽  
Elemental Analyses ◽  
Analgesic Agents ◽  
Ft Ir ◽  
Cox 2 ◽  
Anti Inflammatory

Abstract A new derivatives of isonicotinohydrazide 9 (a-e) and 10(a-e) were designed, synthesized, characterized based on the different spectroscopic analysis FT-IR, -1H, -13C-NMR, mass spectra, and also elemental-analyses, and identified as a remarkable anti-inflammatory along with analgesic effect. In-vitro and in-vivo anti-inflammatory and analgesic actions were performed using analgesic acetic acid-induced squirming and Hot plate latency tests using male Swiss albino mice. The study was supported by the in-silico and ADMET approaches. Among the series, compound (10e) showed the highest IC50 value for COX-1 inhibition, whereas compounds (9e) and (10e) exhibited the highest COX-2 SI. Further, in silico studies provide a putative bind site for the potent compound in a three-dimensional geometrical view. The results revealed that the title compound (10e) with bromo group exhibited potent COX-2 inhibitor at different times which is on par with the normal drug used in the assay system. Substitution of halogens at N’(2-phenoxyacetyl)nicotinohyrazide showed (10e) potent analgesic outcome on acetic acid-induced squirming response and thermal pain among the series 9(a-e) and 10(a-e). The overall pharmacological result suggests that the newly synthesized compounds possess good anti-inflammatory along with analgesic-activity which was evaluated through in-vitro, in-vivo, and --silico studies.

SYNTHESIS, BIOLOGICAL EVALUATION, QSAR AND DOCKING STUDIES OF 2-AMINO-5-(SUBSTITUTED)PHENYL-1,3,4-THIADIAZOLES

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (09) ◽  
pp. 5-12
Author(s):  
S. S Mahajan ◽  
◽  
A. D. Gaitonde
Keyword(s):  
Analgesic Activity ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Qsar Studies ◽  
Paw Oedema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Rat Paw ◽  
Rat Paw Oedema

Ten compounds from the series of 2-amino-5-(substituted)phenyl-1,3,4-thiadiazoles were synthesized and evaluated for anti-inflammatory and analgesic activities. Their structures were characterized by infrared spectroscopy and confirmed by 1H NMR spectroscopy. Anti-inflammatory activity was carried out by carrageenan-induced rat paw oedema method using indomethacin as standard. Analgesic activity was performed by acetic-acid induced writhing method in mice using aspirin as standard. The QSAR studies were performed for the analgesic activity using the software ‘Strike’ from Schrodinger. Docking studies were carried out for COX-2 inhibition using the software ‘Glide’ from Schrodinger. The compounds were obtained in good yields and possessed good anti-inflammatory and analgesic activities. Various physicochemical parameters, contributing towards analgesic activity were identified from the QSAR studies. The Glide Scores were more or less correlated with the anti-inflammatory and analgesic activities of compounds.

Synthesis, Anti-inflammatory, Antimicrobial Potential and Molecular Docking Studies of 4,5-Disubstituted-1,2,4-Triazole Thioacetate Derivatives

2019 ◽  
Vol 16 (7) ◽  
pp. 734-745 ◽  
Author(s):  
Muhammad Nouman Arif ◽  
Humaira Nadeem ◽  
Rehan Zafar Paracha ◽  
Arif-ullah Khan ◽  
Muhammad Imran ◽  
...  
Keyword(s):  
Docking Studies ◽  
Inflammatory Activity ◽  
Biological Assessment ◽  
Maximum Effect ◽  
Docking Analysis ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Rat Paw

Background: In the present study synthesis and biological assessment of nine new ethyl [(4,5-disubstituted- 4H-1,2,4-triazol-3-yl)sulfanyl]acetate derivatives 2(a-i) is performed. Methods: The title compounds were characterized by their analytical and spectral data. All the synthesized compounds were screened for their in vivo anti-inflammatory activity using carrageenaninduced rat paw oedema method and in vitro antimicrobial activity. All the compounds exhibited good anti-inflammatory activity; especially compound 2h produced the maximum effect i.e., 62.5 % comparable to that of standard, diclofenac. The antimicrobial screening results indicated that some of the newly synthesized compounds showed good antibacterial activity, especially against Escherichia coli. Results: All the synthesized thioacetate derivatives of triazoles were also studied for their interactions with the enzymes COX-I and COX-II, two important targets of inflammation pathway, through docking analysis. All the compounds showed good binding affinities with both the enzymes with a maximum value of -8.1 for 2e kcal/mol against COX-I. Conclusion: Docking analysis predicted that our compounds reduce inflammation nonselectively by inhibiting both COX-I and COX-II of inflammatory pathway just like other nonselactive NSAIDS.

Sign in / Sign up

Export Citation Format

Share Document