Inhibition of iNOS by Benzimidazole Derivatives: Synthesis, Docking, and Biological Evaluations

2021 ◽  
Vol 17 ◽  
Author(s):  
Richa Minhas ◽  
Yogita Bansal
Keyword(s):  
Inflammatory Activity ◽  
Benzimidazole Derivatives ◽  
Critical Study ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Inos Inhibitors ◽  
Rat Paw

Background: Inducible nitric Oxide Synthase (iNOS) plays a key role in the progression of inflammatory diseases by accelerating the production of NO, which makes it an intriguing target to treat inflammation in complex diseases. Therefore, the search is on to develop molecules as selective iNOS inhibitors. Objective: The present work was aimed to design, synthesize and evaluate benzimidazole-coumarin coupled molecules as anti-iNOS agents through in silico and pharmacological studies. Methods: A critical study of literature reports on iNOS inhibitors led to the selection of a (un)substituted coumarin nucleus, 2-aminobenzimidazole, and a 4-atom linker as important structural components for iNOS inhibition. Two series of compounds (7-16 and 17-26) were designed and synthesized by coupling these components. The compounds were subjected to docking using iNOS (1QW4) and nNOS (1QW6) as targets. All compounds were evaluated for NO and iNOS inhibitory activities in vitro. The selected compound was finally evaluated for anti-inflammatory activity in vivo using the carrageenan-induced rat paw edema model. Results : All compounds showed moderate to good inhibition of NO and iNOS in vitro. Compound 12 was the most potent inhibitor of NO and iNOS. Hence, it was evaluated in vivo for toxicity and anti-inflammatory activity. It was found to be safe in acute toxicity studies, and effective in reducing the rat paw edema significantly. Its anti-inflammatory behaviour was similar to that of aminoguanidine, which is a selective iNOS inhibitor. Conclusion: The newly synthesized benzimidazole-coumarin hybrids may serve as potential leads for the development of novel anti-iNOS agents.

scholarly journals SYNTHESIS, ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITIES OF ETHYL 2-(2-CYANO-3- (SUBSTITUTED PHENYL)ACRYLAMIDO)-4,5-DIMETHYLTHIOPHENE-3-CARBOXYLATES

2017 ◽  
Vol 10 (7) ◽  
pp. 95 ◽  
Author(s):  
Madhavi K ◽  
Sree Ramya G
Keyword(s):  
Antioxidant Activity ◽  
Free Radical ◽  
Antioxidant Properties ◽  
Inflammatory Activity ◽  
Paw Edema ◽  
Standard Drug ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Rat Paw

Objective: Objective of the study was to synthesize and evaluate a series of novel compounds, ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)- 4,5-dimethylthiophene-3-carboxylates, for in vitro antioxidant and in vivo anti-inflammatory activities.Methods: Ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4,5-dimethylthiophene-3-carboxylates were synthesized by knoevenagel condensation of active methylene group of ethyl 2-(2-cyanoacetamido)-4,5-dimethylthiophene-3-carboxylate with substituted benzaldehydes. The synthesized compounds were evaluated for their in vitro antioxidant properties in three different models, viz., reduction of 1,1-diphenyl-2-pycrylhydrazyl free radical, scavenging of nitric oxide free radical, and ferric ion-induced lipid peroxidation using rat brain homogenate. Few selected compounds with good antioxidant properties were pharmacologically evaluated for anti-inflammatory activity by carrageenan-induced rat paw edema model.Results: Clean and efficient synthetic procedure was used for the preparation of series of compounds. The structures of synthesized compounds were confirmed by infrared, 1H nuclear magnetic resonance and mass spectra. The antioxidant activity data revealed that the compounds of ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4,5-dimethylthiophene-3-carboxylate containing phenolic substitution showed greater antioxidant activity. Hence, the active compounds were evaluated for anti-inflammatory activity and found to possess good activity. The percentage inhibition of rat paw edema obtained for the evaluated compounds was in the range of 70.2-83.1, comparable to the standard drug diclofenac (85.0%).Conclusion: The use of inexpensive, eco-friendly and readily available reagents, easy work-up and high purity of products makes the procedure a convenient and robust method for the synthesis of title compounds. The compounds of ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4,5- dimethylthiophene-3-carboxylate containing phenolic substitution showed greater antioxidant and anti-inflammatory activities.

In vitro and in vivo delivery of atorvastatin: A comparative study of anti-inflammatory activity of atorvastatin loaded copolymeric micelles

2017 ◽  
Vol 32 (8) ◽  
pp. 1127-1138 ◽  
Author(s):  
Sina Andalib ◽  
Pezhman Molhemazar ◽  
Hossein Danafar
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Activity ◽  
Lipid Lowering ◽  
Precipitation Method ◽  
Paw Edema ◽  
Scanning Calorimetry ◽  
Rat Paw Edema ◽  
Anti Inflammatory

Statins have been shown to exert ‘pleiotropic effects’ independent of their cholesterol lowering actions that include anti-inflammatory properties. In this study we synthesized mono methoxy poly (ethylene glycol)–poly (ε-caprolactone) (mPEG-PCL) di block copolymers. The structure of the copolymers was characterized by H nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry and gel permeation chromatography techniques. In this method, atorvastatin was encapsulated within micelles through a single-step nano-precipitation method, leading to the formation of atorvastatin-loaded mPEG-PCL (atorvastatin/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering and atomic force microscopy. In this study the anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles on acute models of inflammation are analyzed, to compare the effect of indometacin in rats. Carrageenan induces rat paw edema; six animals of each group (10 groups) received indometacin, atorvastatin, and atorvastatin/mPEG-PCL micelles orally 1, 6, 12 and 24 h before carrageenan injection in paw. The paw edema thickness measured at 1, 2, 3 and 4 h after injection and percentage inhibition of edema in various groups were calculated. The results showed that the zeta potential of micelles was about −16.6 mV and the average size was 81.7 nm. Atorvastatin was encapsulated into mPEG-PCL micelles with loading capacity of 14.60 ± 0.96% and encapsulation efficiency of 62.50 ± 0.84%. Atorvastatin and atorvastatin/mPEG-PCL micelles showed significant anti-inflammatory activity in the present study. The anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles was significant in comparison with indometacin. Atorvastatin/mPEG-PCL micelles showed more anti-inflammatory activity than atorvastatin. This study revealed the anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles and suggested the statins have a potential inflammatory activity along with its lipid lowering properties. Contrary to anti-inflammatory effects, the pro-inflammatory responses are independent of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition and can be mediated directly by atorvastatin.

scholarly journals EFFECT OF TERPENES AS PENETRATION ENHANCERS ON THE RELEASE AND PERMEATION KINETICS OF MELOXICAM GELS FORMULATIONS

2020 ◽  
pp. 1-5
Author(s):  
Raj Kumari ◽  
Pallavi Matta ◽  
Meenakshi Sharma ◽  
Madhu Verma
Keyword(s):  
Penetration Enhancers ◽  
Peppermint Oil ◽  
Clove Oil ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Lemongrass Oil ◽  
Anti Inflammatory ◽  
Rat Paw

Introduction: The transdermal route of administration has been extensively accepted as one of the potential route for the local and systemic delivery of drugs. The greatest obstacle in drug absorption is the highly organized stratum corneum (SC), which hinder drug transport. The probable solution leads to inclusion of penetration enhancers for reversibly disorganizing the barrier characteristic of stratum corneum. Objective: The main objective of the research work was to study the influence of peppermint oil, lemongrass oil, clove oil and turpentine oil as penetration enhancers on the percutaneous absorption of Meloxicam (ME) from a Carbopol 934 based gel formulation. Materials and Methods: ME gel sample was divided into 5 batches i.e., F1, F2, F3, F4, F5. Except F1, all other batches were incorporated with penetration enhancers (5% w/w) namely peppermint oil, clove oil, lemongrass oil and turpentine oil. The formulations were further evaluated for in-vitro drug release studies using a standard cellophane membrane at 37± 0.5˚ C in phosphate buffer pH 7.4 and a comparative anti-inflammatory activity was conducted using rat paw edema method. Result and Discussion: In-vitro permeation studies using a standard cellophane membrane showed that the rank order of enhancement ratio (ERflux) for Meloxicam as peppermint oil (1.414) > clove oil (1.353) > lemongrass oil (1.326) > turpentine oil (1.272) proving peppermint oil as the most competent penetration enhancer for Meloxicam. Further In- vivo anti-inflammatory activity were carried out using the standard rat paw edema method. The in vivo studies revealed that gel containing peppermint, clove, lemongrass and turpentine exhibited 2.53, 2.0, 1.9 and 1.38 times higher anti-inflammatory effect as compared to meloxicam (standard). Conclusion: It can be concluded from the study that all the 4 terpenes significantly increases the permeation of meloxicam gels and can be used as effective penetration enhancers.

Evaluation of Biological Activity of Derivatives of 1,3,4 Thiadiazole, 1,3,4-Oxadiazole and 1,2,4-Triazole

2020 ◽  
Vol 20 ◽  
Author(s):  
Gaurav M. Doshi ◽  
Mayuresh U. Bansode ◽  
Rakesh R. Somani
Keyword(s):  
Erythrocyte Membrane ◽  
Paw Edema ◽  
Toxic Dose ◽  
Rat Paw Edema ◽  
Maximum Decrease ◽  
Inhibitory Activities ◽  
Anti Inflammatory ◽  
Rat Paw

Objectives: 1,3,4-thiadiazole (A), 1,3,4-oxadiazole (B) and 1,2,4-triazole (C) derivatives have been known for their immense pharmacotherpaeutic potential. The current research article attempts to further explore and understand the probable biochemical mechanism related to anti-inflammatory activity of derivatives. Methods: The screened A, B and C derivatives were investigated for both in-vitro (Erythrocyte Membrane stabilization activity, Proteinase enzyme inhibitory activities) and in-vivo correlation using acute and chronic anti-inflammatory potential by carrageenan induced rats paw edema and cotton pellet granuloma methods respectively. The activity was studied after interpreting acute toxicity studies results. Results: In vitro studiesin the case of Erythrocyte Membrane stability and Proteinase enzyme inhibitory activities exhibited by A, B, and C at 100 ppm were found to be 48.89%, 51.08% and 50.08% and 66.78%, 76.91% and 57.41% respectively. The maximum toxic dose was found to be 2000 mg/kg. The derivatives were studied for two-dose levels viz; Lower (100 mg/kg) and higher dose (200 mg/kg). In rat paw edema maximum decrease was obtained for A (50.05%), B (50.05%) and C (51.06%) at lower and higher dose at 68.76%, 55.61%, and 65.26% respectively for effect up to 24 h. In the chronic model of cotton pelletgranuloma viz; higher and lower doses of A, B and C exhibited 38.15%, 33.19% and 30.25 % and 19.45%, 18.55% and 17.55 % respectively. Conclusion: The studied models depicted that derivatives A, B and C have the probable potential as anti-inflammatory agents. Further studies need to undertaken to explore their potential in the different therapeutic areas.

scholarly journals Anti-allergic and anti-inflammatory activities of black cumin extracts in in vitro and in vivo model systems

2021 ◽  
Author(s):  
Nazma Shaheen ◽  
Afiatul Azam ◽  
Amlan Ganguly ◽  
Saeed Anwar ◽  
Md Sorwer Alam Parvez ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Paw Edema ◽  
Writhing Test ◽  
Black Cumin ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Dose Dependent

Black cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including anti-allergic, bronchial asthma, and anti-inflammatory properties. We sought to evaluate BC extracts' efficacy for their anti-allergic and anti-inflammatory properties using a comprehensive in vitro, in vivo, and silico experimental setup. To investigate whether BC extract has anti-inflammatory, anti-allergic, and analgesic therapeutic potentials in vitro and in vivo. The activity of BC was assessed through anti-allergic activity on rat basophilic leukemia-2H3 cell line, anti-inflammatory activity on J774.1A cell line, anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test, and ingenuity analysis of the BC extracts in inflammation control. BC exerted potent anti-allergic activity by inhibiting antigen-induced degranulation. An anti-inflammatory effect is shown by inhibiting TNF-α pro-duction. The acetic acid-induced writhing test shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test shown the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation. This study suggests that bioactive compounds in BC extract act as an anti-allergic and anti-inflammatory agent by regulating several downstream and upstream inflammation pathways.

scholarly journals Evaluation of in vivo anti-inflammatory activity of Ariflex tablet in comparison with diclofenac and aceclofenac tablet in carrageenan induced rat paw edema model

2021 ◽  
Vol 9 (10) ◽  
pp. 2966
Author(s):  
Sanjay Nipanikar ◽  
Sohan S. Chitlange
Keyword(s):  
Lateral Malleolus ◽  
Inflammatory Activity ◽  
Control Group ◽  
Paw Edema ◽  
Surgical Interventions ◽  
Locomotor Disability ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Rat Paw

Background: Osteoarthritis is a major cause of pain and locomotor disability worldwide. Though various pharmacological, mechanical and surgical interventions are used, there is no known cure for OA. The present study was conducted to evaluate anti-inflammatory activity of Ariflex tablet (conceptualized and developed by Ari Healthcare Pvt. Ltd.) in comparison with diclofenac and aceclofenac tablet in carrageenan induced rat paw edema model.Methods: Wistar rats of either sex weighing 150-180 g were taken and divided into 4 groups with 6 animals in each group i.e. group 1 (control group), group 2 (diclofenac tablet), group 3 (aceclofenac tablet) and group 4 (ariflex tablet). The study drugs were orally administered with feeding needle, 30 minutes prior to carrageenan injection. After 30 min 1% w/v of 0.05 ml carrageenan was injected subcutaneously in the rat paw. The paw was marked with ink at the level of lateral malleolus and immersed in mercury up to lateral malleolus mark. The paw volume was measured plethysmographically after injection at 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour and eventually at 5 hour.Results: All the test formulations possess statistically significant (p<0.05) anti-inflammatory activity as compared to control group. The maximum percentage inhibition for Ariflex tablet was 96.97% at the end of 5 hours. When compared to control group, statistically significant reduction of paw edema was observed. The anti-inflammatory activity of Ariflex tablet from 2 hours onwards is comparable to that of diclofenac tablet and aceclofenac tablet.Conclusions: Ariflex tablet possesses significant anti-inflammatory activity.

scholarly journals ANTI-INFLAMMATORY PROFILING OF SEED AND RIND EXTRACTS OF AMOMUM SUBULATUM

2020 ◽  
pp. 204-208
Author(s):  
SUPRIYA AGNIHOTRI
Keyword(s):  
Inflammatory Activity ◽  
In Vivo Studies ◽  
Inflammatory Models ◽  
Rat Paw Edema ◽  
Soxhlet Apparatus ◽  
Anti Inflammatory ◽  
Amomum Subulatum ◽  
Rat Paw

Objective: The study aimed to evaluate the anti-inflammatory activity of Amomum subulatum (greater cardamom) seed and rind extracts in Wistar rats. Methods: The seed and rind of A. subulatum were air-dried in the shade, powdered, and subjected to 80% hydroalcoholic extraction in the Soxhlet apparatus. The anti-inflammatory activity of the seed and rind extracts of A. subulatum was evaluated by in vivo and in vitro methods. Results and Discussion: In vivo studies, namely, carrageenan-induced rat paw edema, cotton pellet granuloma, and formaldehyde-induced arthritis model confirmed the anti-inflammatory potential of seed and rind extracts of A. subulatum. It was found that rind extract exhibited better inhibition of inflammation as compared to seed extract. A. subulatum rind extract at the dose of 500 μg/ml exhibited best results for in vitro studies, namely, inhibition of albumin denaturation (73% inhibition), antiproteinase action (58% inhibition), membrane stabilization, heat-induced hemolysis, hypotonicity-induced hemolysis (54% inhibition), anti-lipoxygenase activity. Conclusions: The results of the study showed that the rind extract of A. subulatum (greater cardamom) possesses significant anti-inflammatory potential in various in vivo and in vitro anti-inflammatory models in the experimental animals.

scholarly journals Synthesis and Evaluation of Anti-inflammatory Activity of some Thiazolo[4,5-b]pyridines

2021 ◽  
Vol 12 (6) ◽  
pp. 7226-7238
Keyword(s):  
Mass Spectrometry ◽  
1H Nmr Spectroscopy ◽  
Functional Model ◽  
Inflammatory Activity ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Acylation Reactions

The 18 new thiazolo[4,5-b]pyridin-2-one derivatives have been synthesized using alkylation, cyanethylation, hydrolysis, and acylation reactions. The structures of the obtained compounds have been confirmed by 1H NMR spectroscopy, mass spectrometry, and elemental analysis. The study of the in vivo anti-inflammatory activity of the synthesized substances was assessed by using the functional model of carrageenan-induced rat paw edema. The present results of anti-inflammatory activity have shown that the synthesized compounds demonstrated considerable anti-inflammatory effects. Some of them approach or exceed the comparative drug Ibuprofen in terms of activity.

scholarly journals Synthesis of some new thiazolo[4,5-b]pyridin-2-ones and research of their anti-inflammatory activity

2019 ◽  
pp. 52-60
Author(s):  
T. I. Chaban
Keyword(s):  
Acetic Acid ◽  
Structural Modification ◽  
Acid Hydrazide ◽  
Inflammatory Activity ◽  
In Vivo Studies ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Rat Paw

In modern theoretical and clinical medicine inflammation problem remains one of the main.Deregulation of inflammatory processes leads to specific pathologies.There is a significant amount of drugs used to treat inflammation. But all of them have varying degrees of ulcerogenic properties. To overcome these limitations search is ongoing throughout the World to find new effective and safe anti-inflammatory agent. Therefore, of course, the synthesis of thiazolidines annelated with the pyridine cycle and the study of their anti-inflammatory properties is an interesting and relevant area. The objective of the present work was to synthesize a series of novel thiazolo[4,5-b]pyridine-2-ones by the structural modification of the (5,7-dimethyl-2-oxo-thiazolo[4,5-b]pyridine-3-yl)-acetic acid hydrazide for further pharmacological screening in vivo as anti-inflammatory activities. The objects of the study were thiazolo[4,5-b]pyridines, obtained by the structural modification of the (5,7-dimethyl-2-oxo-thiazolo[4,5-b]pyridine-3-yl)-acetic acid hydrazide. Anti-inflammatory activity was evaluated using carrageenan induced rat paw edema method in rats In vivo studies were carried out  for anti-inflammatory activity employing the carrageenan-induced rat paw edema method. Anti-inflammatory activity was defined by measuring the paw edema volume 4 h after the carrageenan injection.The NSAID drug Ibuprofen in effective therapeutic doses were tested inparallel as an activity references. Inhibition of the inflammatory response was expressed as a percentage of the paw volume reduction. Studies of anti-inflammatory activity showed that the synthesized compounds had pronounced diuretic properties, and some of them according to activity indicators were approaching or exceeding comparative preparations. The results of the anti-inflammatory activity of the synthesized compounds derivatives (5,7-dimethyl-2-oxo-thiazolo[4,5-b]pyridine-3-yl)-acetic acid hydrazide show the potential for the search for anti-inflammatory agents among thiazolo[4,5-b]pyridine-2-ones.

scholarly journals EVALUATION OF ANTI-INFLAMMATORY (IN VIVO) ACTIVITY OF ARIFLEX LINIMENT IN COMPARISON WITH DICLOFENAC GEL IN CARRAGEENAN INDUCED RAT PAW EDEMA MODEL

2021 ◽  
pp. 67-70
Author(s):  
SANJAY NIPANIKAR ◽  
S. S. CHITLANGE
Keyword(s):  
Significant Inhibition ◽  
Lateral Malleolus ◽  
Inflammatory Activity ◽  
Control Group ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Edema Model ◽  
Anti Inflammatory ◽  
Rat Paw

Objective: The present study was conducted to evaluate anti-inflammatory activity of Ariflex liniment (conceptualized and developed by Ari Healthcare Pvt. Ltd) in comparison with Diclofenac gel in carrageenan induced rat paw edema model. Methods: Wistar rats of either sex weighing 150-180 g were taken and divided into 3 groups with 6 animals in each group i.e. Group 1 (Controlled Group), Group 2 (Diclofenac gel) and Group 3 (Ariflex liniment). The study drugs were topically applied 30 min prior to carrageenan injection. After 30 min 1% w/v of 0.05 ml carrageenan was injected subcutaneously in the paw. The paw was marked with ink at the level of lateral malleolus and immersed in mercury up to the lateral malleolus mark. The paw volume was measured plethysmographically, immediately after injection i.e. on 0 min, and then on 30 min,1h, 2h,3h, 4h and 5hr after injection. Results: Diclofenac gel sodium treated group showed significant inhibition (p<0.01) of paw edema at 30 min, 1, 2, 3, 4 and 5th hrs as compared to control group. Ariflex Liniment showed significant inhibition (p<0.05) of paw edema at 30 min, 1, 2, 3, and 4th hrs as compared to the control group. Group treated with Ariflex Liniment did not show any significant decrease in paw edema volume at 5th hrs when compared to the control group. Conclusion: Ariflex Liniment possesses anti-inflammatory activity.

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