scholarly journals Synthesis of Some New Acetanilide Derivatives as COX Inhibitors and Assessment of Analgesic/ Anti-Inflammatory Activities

2021 ◽  
Vol 37 (6) ◽  
pp. 1475-1487
Author(s):  
Rajib Kumar Singh ◽  
Arvind Kumar ◽  
Arun K. Mishra
Keyword(s):  
Diclofenac Sodium ◽  
Docking Studies ◽  
Laboratory Animals ◽  
In Vivo Evaluation ◽  
Activity Evaluation ◽  
Physiochemical Parameters ◽  
Cox 2 ◽  
Anti Inflammatory

The purpose of the present research was to synthesize a new series of acetanilide derivatives that would have analgesic and anti-inflammatory properties in laboratory animals (rats). IR spectroscopy, 1HNMR spectroscopy and Mass spectroscopy were used to confirm the structures of freshly synthesised compounds. The goal of the computer analysis of synthesized compounds was to see how similar they were in terms of physicochemical properties. For this, physiochemical parameters were calculated. The result suggested the reasonable physiochemical similarity with diclofenac sodium and Indomethacin. Molecular docking studies showed that the all the test compounds perfectly docked with COX-2 enzyme with all the drug-likeness characteristics. Before start of in-vivo evaluation, in vitro cyclooxygenase (COX) inhibition assays was performed with an aim to evaluate the compounds against the protein target COX-2 which would exhibit their inhibitory activity. The test compounds (C1-C6) were subjected to analgesic activity evaluation by Eddy’s hot plate method and anti-inflammatory activity evaluation by Carageenan induced edema method respectively.

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 Syringol Isolated From Eleusine Coracana (L.) Gaertn Bran Suppresses Inflammatory Response Through the Down-Regulation of cPLA2, COX-2, IκBα, p38 and MPO Signaling in sPLA2 Induced Mice Paw Edema.

2021 ◽  
Author(s):  
Mallanayakanakatte D. Milan Gowda ◽  
Jayachandra K ◽  
Vikram Joshi ◽  
Vaddarahally N. Manjuprasanna ◽  
Gotravalli V. Rudresha ◽  
...  
Keyword(s):  
Docking Studies ◽  
Eleusine Coracana ◽  
Ion Concentration ◽  
Western Blots ◽  
Inflammatory Molecule ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Calcium Ion Concentration

Abstract Eleusine coracana (L.) Gaertn (E. coracana) is one of the highest consuming food crops in Asia and Africa. E. coracana is a plant with several medicinal values including anti-ulcerative, anti-diabetic, anti-viral and anti-cancer properties. However, the anti-inflammatory property of E. coracana remains to be elucidated. Therefore, the objective of present study was to investigate the potential in isolated molecule from E. coracana via a combination of in vitro, in vivo and in silico methods. In this study we have isolated, purified and characterized an anti-inflammatory molecule from E coracana bran extract known as syringol. Purification of syringol was accomplished by combination of GC-MS and RP-HPLC techniques. Syringol significantly inhibited the enzyme activity of sPLA2 (IC50 = 3 µg) and 5-LOX (IC50 = 0.325 µg) in vitro. The inhibition is independent of substrate concentration, calcium ion concentration and was irreversible. Syringol interacts with purified sPLA2 enzymes as evidenced by fluorescence and molecular docking studies. Further, the syringol molecule dose dependently inhibited the development of sPLA2 and carrageenan induced edema. Furthermore, syringol decreases the expression of cPLA2, COX-2, IκBα, p38 and MPO in edematous tissues as demonstrated by western blots. These studies revealed that syringol isolated from E coracana bran may develop as a potent anti-inflammatory molecule.

scholarly journals In vitro and In vivo Anti-inflammatory Activity of the Extracts of Whole Plant Argyreia imbricata (Roth) Sant. & Patel

2020 ◽  
Vol 11 (4) ◽  
pp. 7317-7322
Author(s):  
Sebastin V ◽  
Gopalakrishnan G ◽  
Sreejith M ◽  
Anoob Kumar K I
Keyword(s):  
Ethyl Acetate ◽  
Diclofenac Sodium ◽  
Inflammatory Activity ◽  
Albino Rats ◽  
Significant Activity ◽  
In Vivo Evaluation ◽  
Whole Plant ◽  
Anti Inflammatory

Plants of the genus Argyreia have ethnomedicinal importance, and several pharmacological activities are also reported. In this study, the anti-inflammatory activity of different extracts of Argyreia imbricata was evaluated by in vitro and in vivo methods. In both evaluations, standard, Diclofenac sodium was used for comparative evaluation. In this study, extraction of powdered whole plant material was done with different solvents viz., petroleum ether, chloroform, ethyl acetate and methanol by soxhelation. In vitro anti-inflammatory activity of all the prepared extracts was evaluated by stabilization of human red blood cell (HRBC) membrane in different temperature and tonicity conditions. Among the six different concentrations of four tested extracts, the ethyl acetate and methanol extracts (1000μg/ml) showed significant activity in the in vitro evaluation. They were selected for the in vivo evaluation on the paw oedema induced by carrageenan on Wistar albino rats. Two doses, 200mg.kg-1 and 400mg.kg-1 of the test extracts were subjected to evaluation. Both the tested extracts showed the activity, particularly, the methanol extract in the dose of 400mg.kg-1 showed significant activity. Results of this study strongly supported the anti-inflammatory activity of the tested extracts. Further, studies on toxicity, identification, isolation of the active constituents may give useful results.

Design, Synthesis, Antioxidant, Anti-inflammatory Activity and Molecular Docking Studies of Novel 3,4,5-Trisubstituted-1,2,4-Triazole Derivatives Bearing Benzimidazole Moiety

2020 ◽  
Vol 17 ◽  
Author(s):  
Ramamurthy Katikireddy ◽  
Ramu Kakkerla ◽  
M.P.S. Murali Krishna ◽  
Gandamalla Durgaiah ◽  
Narasimha Reddy Yellu
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Biological Data ◽  
Inflammatory Activity ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Cox 2 ◽  
Anti Inflammatory

: 5-(7-Methyl-2-propyl-1H-benzo[d]imidazol-5-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols(6a-i) have been synthesized from key intermediate 7-methyl-2-propyl-1H-benzo[d]imidazole-5-carbohydrazide(3). The hydrazide was treated with different aryl isothiocyanatesto give corresponding thiosemicarbazone derivatives, which underwent cyclization in 4N sodium hydroxide to affordcorresponding title compound. All the compounds evaluated for their in vitro antioxidant and in vivo anti-inflammatory activity. From the results, compounds 6b and 6e have shown potential antioxidant and anti-inflammatory activity. The biological data was further supported by molecular docking studies, which revealed the binding pattern and the affinity of the molecules in the active site of COX-2.

In vitro and in vivo evaluation of the anti-inflammatory effects of Arzanol from Helichrysum italicum

Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
Anti Inflammatory

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF CURCUMIN AND CAPSAICIN AUGMENTED IN COMBINATION

2017 ◽  
Vol 9 (6) ◽  
pp. 145
Author(s):  
Thriveni Vasanth Kumar ◽  
Manjunatha H. ◽  
Rajesh Kp
Keyword(s):  
Acetic Acid ◽  
Protective Effect ◽  
Vascular Permeability ◽  
Diclofenac Sodium ◽  
Significant Inhibition ◽  
Inflammatory Activity ◽  
Anti Inflammatory ◽  
The Individual

Objective: Dietary curcumin and capsaicin are well known for their health beneficial potencies. The current study was done to assess the anti-inflammatory activity of curcumin, capsaicin and their combination by employing in vitro and in vivo models.Methods: We investigated the protective effect of curcumin, capsaicin and their combination using in vitro heat induced human red blood cell (HRBC) membrane stabilisation, in vivo 3% agar induced leukocyte mobilisation and acetic acid induced vascular permeability assay.Results: Curcumin, capsaicin and their combination exhibited concentration dependent protective effect against heat-induced HRBC membrane destabilisation, while combined curcumin and capsaicin restored 87.0±0.64 % membrane stability and it is found to be better than curcumin, capsaicin and diclofenac sodium (75.0±0.25. 72±0.9 and 80.0±0.31 %) protective effect. In agar suspension induced leukocyte mobilization assay, the combined curcumin and capsaicin had shown 39.5±1.58 % of inhibition compared to individual curcumin and capsaicin, which showed moderate inhibition of 16.0±3.14 and 21.6±2.17 % respectively. Besides, the combined curcumin and capsaicin had shown highly significant inhibition of acetic acid-induced vascular permeability in rats (62.0±3.14 %), whereas individual curcumin and capsaicin showed moderate inhibition of vascular permeability with 36.0±2.41 and 43.0±1.92 % respectively.Conclusion: This study demonstrates the significant anti-inflammatory property of combined curcumin and capsaicin at half of the individual concentration of curcumin and capsaicin.

scholarly journals Ketorolac-dextran conjugates: Synthesis, in vitro and in vivo evaluation

2007 ◽  
Vol 57 (4) ◽  
pp. 441-450 ◽  
Author(s):  
Savita Vyas ◽  
Piyush Trivedi ◽  
Subhash Chaturvedi
Keyword(s):  
Human Plasma ◽  
Parent Drug ◽  
Aqueous Solubility ◽  
Spectrophotometric Analysis ◽  
In Vivo Evaluation ◽  
Gastrointestinal Side Effects ◽  
Molecular Masses ◽  
Anti Inflammatory

Ketorolac-dextran conjugates: Synthesis,in vitroandin vivoevaluationKetorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. Invitrohydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics.In vivobiological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

scholarly journals Synthesis and biological evaluation of some novel pyrazolopyrimidines incorporating a benzothiazole ring system

2013 ◽  
Vol 63 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Mohammed Afzal Azam ◽  
Loganathan Dharanya ◽  
Charu Chandrakant Mehta ◽  
Sumit Sachdeva
Keyword(s):  
Antimicrobial Activity ◽  
Diclofenac Sodium ◽  
Biological Evaluation ◽  
Ring System ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Pyrimidine Moiety ◽  
Synthesis And Biological Evaluation

In the present study, a series of benzothiazol derivatives 3a-l containing pyrazolo[3,4-d]pyrimidine moiety at the second position were synthesized and characterized by analytical and spectral data. The compounds were tested for their in vitro antimicrobial activity. Compounds 1-(1,3-benzothiazol-2- yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine (3a), 1- (1,3-benzothiazol-2-yl)-4-(4-chlorophenyl)-3-methyl-1H-pyrazolo[ 3,4-d]pyrimidine (3d) and 1-(1,3-benzothiazol-2-yl)- 3-methyl-4-substituted phenyl-1H-pyrazolo[3,4-d]pyrimidines (3h-j) showed significant inhibitory activity against P. aeruginosa whereas compounds 1-(1,3-benzothiazol-2-yl)-4- (2-chlorophenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine (3b), 2-[1-(1,3-benzothiazol-2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin- 4-yl]phenol (3e), 1-(1,3-benzothiazol-2-yl)-4-(3,4-dimethoxyphenyl)- 3-methyl-1H-pyrazolo[3,4-d]pyrimidine (3h), 4-[1-(1,3-benzothiazol-2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyri midin-4-yl]-N,N-dimethylaniline (3j) and 1-(1,3-benzothiazol- 2-yl)-3-methyl-4-[2-phenylvinyl]-1H-pyrazolo[3,4-d]pyrimidine (3k) were found to be active against C. albicans. Some of these synthesized compounds were evaluated for their in vivo acute toxicity, analgesic, anti-inflammatory, and ulcerogenic actions. The tested compound 4-[1-(1,3-benzothiazol- 2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-N, N-dimethylaniline (3j) exhibited maximum analgesic and anti-inflammatory activities. Compounds 1-(1,3-benzothiazol- -2-yl)-3-methyl-4-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidine (3i) and 3j showed a significant gastrointestinal protection compared to the standard drug diclofenac sodium.

2,5-disubstituted-4-thiazolidinones: Synthesis, anti-inflammatory, free radical scavenging potentials and structural insights through molecular docking

2021 ◽  
Vol 18 ◽  
Author(s):  
Jagseer Singh ◽  
Pooja A Chawla ◽  
Rohit Bhatia ◽  
Shamsher Singh
Keyword(s):  
Free Radicals ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Assay Method ◽  
Acidic Group ◽  
Active Compounds ◽  
Cox 2 ◽  
Anti Inflammatory

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

scholarly journals Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors

2020 ◽  
Vol 21 (24) ◽  
pp. 9623
Author(s):  
Łukasz Szczukowski ◽  
Edward Krzyżak ◽  
Adrianna Zborowska ◽  
Patrycja Zając ◽  
Katarzyna Potyrak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
One Pot ◽  
Design Synthesis ◽  
Biological Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Dna Strand ◽  
Cox 2 Inhibitors

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

Sign in / Sign up

Export Citation Format

Share Document