Reference Drug Ibuprofen Research Articles

Synthesis of Some New 7-(arylidene/heteroylidene imino)-2-(3,4-dimethoxy-phenyl)-5-oxo- 1,5-dihydro-[1,2,4]triazolo[1,5-α]pyridine-6-carbonitrile Derivatives as Potent Antibacterial and Anti-inflammatory Agents

A new series of 7-(arylidene/heteroylidene imino)-2-(3,4-dimethoxy-phenyl)-5-oxo-1,5-dihydro-[1,2,4] triazolo[1,5-α]pyridine-6-carbonitrile derivatives i.e., Schiff bases (4a-4j) was synthesized from reaction of 7-amino-2-(3,4-dimethoxy-phenyl)-5-oxo-1,5-dihydro-[1,2,4]triazolo[1,5-α]pyridine-6-carbonitrile (3) with substituted benzaldehydes or hetraldehydes in presence of glacial acetic acid. The antibacterial and anti-inflammatory properties of compounds 3, 4a-4j were investigated, and the results showed that some of the synthesized compounds had better activity than the standard reference drugs. The minimum inhibitory concentration of compounds 4b, 4c, 4f, 4g, and 4i was found to be 10 μg/mL, which was lower than that of ciprofloxacin. The compounds were also tested for anti-inflammatory properties in vitro, and compounds 4a and 4f were found to have superior anti-inflammatory action at 100 μg/mL compared to the standard reference drug ibuprofen.

Synthesis of Some New 7-(arylidene/heteroylidene imino)-2-(3,4-dimethoxy-phenyl)-5-oxo- 1,5-dihydro-[1,2,4]triazolo[1,5-α]pyridine-6-carbonitrile Derivatives as Potent Antibacterial and Anti-inflammatory Agents

A new series of 7-(arylidene/heteroylidene imino)-2-(3,4-dimethoxy-phenyl)-5-oxo-1,5-dihydro-[1,2,4] triazolo[1,5-α]pyridine-6-carbonitrile derivatives i.e., Schiff bases (4a-4j) was synthesized from reaction of 7-amino-2-(3,4-dimethoxy-phenyl)-5-oxo-1,5-dihydro-[1,2,4]triazolo[1,5-α]pyridine-6-carbonitrile (3) with substituted benzaldehydes or hetraldehydes in presence of glacial acetic acid. The antibacterial and anti-inflammatory properties of compounds 3, 4a-4j were investigated, and the results showed that some of the synthesized compounds had better activity than the standard reference drugs. The minimum inhibitory concentration of compounds 4b, 4c, 4f, 4g, and 4i was found to be 10 μg/mL, which was lower than that of ciprofloxacin. The compounds were also tested for anti-inflammatory properties in vitro, and compounds 4a and 4f were found to have superior anti-inflammatory action at 100 μg/mL compared to the standard reference drug ibuprofen.

Anti-Inflammatory Activity Evaluation of the Extract and Topical Pre-Formulation of Morus nigra Fruits

Natural products are often a source for bioactive compounds which have great potential for developing novel therapeutic agents. In this sense, the present study aimed to formulate and evaluate a gel containing Morus nigra leaf extract and to evaluate its anti-inflammatory (in-vivo) and antioxidant (in-vitro) activity. The anti-inflammatory activity was evaluated using Carrageenan-induced paw oedema. The antioxidant activity is evaluated by the lipid peroxidation inhibition and DPPH radical scavenging method. The results indicated that the extract (oral and topical route) and the blackberry gel (topical route) produced a significant anti-inflammatory activity (p < 0.05) compared to the untreated control, and similar to the reference drugs (ibuprofen and diclofenac). Regarding antioxidant activity, the Morus nigra extract also showed a significant activity in the tested models. Based on the above observations and results, mora gel formulation was found to be a promising anti-inflammatory formulation and further extensive in-vitro and in-vivo studies are warranted to evaluate its safety and biological potency and which may be useful for further clinical applications.

New NSAID Conjugates as Potent and Selective COX-2 Inhibitors: Synthesis, Molecular Modeling and Biological Investigation.

New sets of ibuprofen and indomethacin conjugates comprising triazolyl heterocycle were synthesized via click chemistry, adopting an optimized protocol through the molecular hybridization approach affording the targeted agents in good yields. The new non-steroidal anti-inflammatory drug (NSAID) conjugates were designed and synthesized and could be considered as potential drug candidates for the treatment of pain and inflammation. The anti-inflammatory properties were investigated for all the synthesized conjugates. Among 14 synthesized conjugates, four (5a, 5b, 5d, and 5e) were found to have significant anti-inflammatory properties potency 117.6%, 116.5%, 93.8%, and 109.1% in comparison to reference drugs ibuprofen (97.2%) and indomethacin (100%) in the rat paw edema carrageenan test without any ulcerogenic liability. The suppression effect of cytokines IL-6, TNF-α, and iNOS in addition to NO in the LPS-induced RAW264.7 cells supports the promising anti-inflammatory properties observed in the ibuprofen conjugates. In addition, several conjugates showed promising peripheral and central analgesic activity. The selectivity index (SI) of compound 5a (23.096) indicates the significant efficacy and selectivity for COX-2 over COX-1. Molecular modeling (docking and QSAR) studies described the observed biological properties.

Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives.

(1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of inflammation; (2) Methods: we designed and synthesized 23 mollugin derivatives and evaluated their inhibitory activity against NF-κB transcription; (3) Results: Compound 6d exhibited the most promising inhibitory activity (IC50 = 3.81 µM) and did not show any significant cytotoxicity against the tested cell lines. Investigation of the mechanism of action indicated that 6d down-regulated NF-κB expression, possibly by suppressing TNF-α-induced expression of the p65 protein. Most of the compounds exhibited potent anti-inflammatory activity. Compound 4f was the most potent compound with 83.08% inhibition of inflammation after intraperitoneal administration, which was more potent than mollugin and the reference drugs (ibuprofen and mesalazine). ADMET prediction analysis indicated that compounds 6d and 4f had good pharmacokinetics and drug-like behavior; (4) Conclusions: Several series of mollugin derivatives were designed, synthesized, and evaluated for NF-κB inhibitory activity and toxicity. These results provide an initial basis for the development of 4f and 6d as potential anti-inflammatory agents.

A Study on Anti-inflammatory Activity of Stem Bark Extract of Holoptelea integrifolia

Background: Holoptelea integrifolia has been used for a long time in traditional medicine to cure inflammatory pain. The goal of the current research was to consider the anti-inflammatory activity and phytochemicals study of both the extracts of the stem bark of Holoptelea integrifolia. Methods: Anti-inflammatory potential was figure out in Carrageenan and Histamine models at 200 mg/kg doses. Apart from this, we have evaluated parameters like paw edema body weight, locomotor activity, hematological, biochemical assessment, etc. Results: Qualitative chemical test investigation of both the extracts of H. integrifolia stem bark acknowledge the presence of proteins, amino acids, alkaloids, glycosides, tannins, and flavenoids. The 200 mg/kg, p.o dose of the extract showed remarked (P < 0.05) dose-dependent inhibition of edema formation. Both the ethanolic extract (200 mg/ kg, b. w) and aqueous extract (200 mg/ kg, b. w) of H. integrifolia stem bark showed remarked anti-inflammatory properties in comparison to reference drug Ibuprofen. In the Carrageenan model, the ethanolic extract has good anti-inflammatory activity than the aqueous extract. So, the ethanolic extract of stem bark of H. integrifolia is used to combat inflammation alone or with other conventional anti-inflammatory agents to treat different inflammatory disorders. Conclusion: Taken together, these results support the traditional use of Holoptelea integrifolia as a potent anti-inflammatory agent that may be proposed for the treatment of inflammatory pain.

An in vivo evaluation of anti-inflammatory, analgesic and anti-pyretic activities of newly synthesized 1, 2, 4 Triazole derivatives

BackgroundIn recent years, 1, 2, 4-triazole and its derivatives have been reported to be pharmacologically significant scaffolds. They possess analgesic, anti-tubercular, anti-inflammatory, anti-convulsant, anti-oxidant, anti-fungal, anti-cancer, anxiolytic and anti-depressant activity. This study was designed and conducted to evaluate the potential anti-inflammatory, analgesic and antipyretic activities of Triazole derivatives.MethodsSwiss albino (male and female) mice weighing 20-30 g (10-24 weeks female), (5-14 weeks male) and Wister Kyoto rats (male and female) weighing 200-300 g (8-10 weeks old) were used for the present study. Anti-inflammatory activity was checked using Lambda carrageenan (λ) and egg albumin-induced paw edema models. Analgesic via Writhing Reflex induced by acetic acid and formalin, furthermore anti-pyretic activity was assessed by yeast induced pyrexia.ResultsBoth of the test compounds exhibited encouraging anti-inflammatory analgesic and antipyretic results when compared with standard drug ibuprofen. The maximum inhibition of edema for the compound (S)-1-(4-Amino-5-mercapto-4H-1,2,4-triazole-3-yl) ethanol [3] was found to be (91)% as compared to reference drug ibuprofen (82)%, while (S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol [5e] showed equipotent results to ibuprofen (81)%. The derivatives were also screened for their anti-nociceptive activity by Acetic acid writhing and tail immersion test. Compound 3 showed a significant reduction in wriths (83)% as compared to standard drug ibuprofen 71.5% and [5] showed comparable results to ibuprofen by exhibiting 70% reduction in writh at the same dose as that of standard drug, moreover, there were no signs of toxicity being observed after administration of high doses of test compounds to mice.ConclusionsIt is evident from the results that compounds 3(compound A) and 5(compound B) are a potential candidate for anti-inflammatory, analgesic and anti-pyretic and the scaffold could be used for further structural modifications. Further studies would help to evaluate their molecular mechanism of action regarding these beneficial activities.

Assessment of pharmacological activities of Lygodium microphyllum Cav. leaves in the management of pain, inflammation, pyrexia, diarrhea, and helminths: In vivo, in vitro and in silico approaches

Lygodium microphyllum Cav. (Family: Lygodiaceae) is a perennial, snake fern and an invasive weed in Florida and also known as old world climbing fern. This study is intended to evaluate the antipyretic, analgesic, anti-inflammatory, antidiarrheal and anthelmintic activity of methanol extract of Lygodium microphyllum Cav. leaves (MELM) by in vivo, in vitro and in silico approaches. In addition, Biovia, PyRx autoDock Vina, UCSF Chimera have been applied to investigate the docking study in order to evaluate the binding interaction and an online tool was used to explore the ADME/T properties of selected bioactive compounds. In acetic acid induced writhing study, MELM inhibited 44.28% and 56.61% of writhes at 200 and 400 (mg/kg) respectively compared to standard drug Diclofenac-Na (10 mg/kg) (74.42% inhibition). In anti-inflammatory experiment by formalin triggered licking method, MELM caused significant (p < 0.05) inhibition of licking in both early phase (42.97%, 63.30%) and late phase (43.35%, 63.03%) at the doses of 200 and 400 mg/kg respectively, whereas reference drug Ibuprofen inhibited paw licking 77.18% in early phase and 76.86% in late phase. MELM also showed promising antipyretic potential where the maximum reduction of fever was produced by MELM 400 mg/kg whose fever lowering capacity is close to the prescribe drug Indomethacin 4 mg/kg, i.p. In Castor oil triggered diarrhea method, MELM delayed the onset time of diarrhea, continuous persistence of wet feces, and decreased the weight of wet feces remarkably. Defection inhibition was achieved 27.56% and 51.72%, for MELM 200 and at 400 (mg/kg) respectively while loperamide 2 (mg/kg) yields 55.17% inhibition of the diarrheal defecation. In anthelmintic bioassay, MELM took 5.83 ± 0.83 and 41.67 ± 1.78 min respectively for paralyzing and death compared to standard drug albendazole; (paralysis time 4.00 ± 0.73 min and death time 31,00 ± 1.71 min). Isoeleutherol, isoquercetin and quercetin were found prominent in molecular docking study and ADME/T analysis verified their drug likeliness. The research validates the moderate analgesic, anti-inflammatory, and remarkable antipyretic, antidiarrheal, anthelmintic activities of the plant extract which can be used an alternative source of novel therapeutics.

Anti-inflammatory Flavanones and Flavones from Tephrosia linearis.

Phytochemical analysis of a methanol-dichloromethane (1:1) extract of the aerial parts of Tephrosialinearis led to the isolation of 18 compounds. Seven of these, namely, lineaflavones A-D (1-4), 6-methoxygeraldone (5), 8″-acetylobovatin (6), and 5-hydroxy-7-methoxysaniculamin A (7) are new compounds. The compounds were characterized based on their NMR and HRMSn data. The anti-inflammatory effects of the crude extract and isolated compounds were evaluated by measuring the levels of interleukins (IL-1β, IL-2, and IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). The crude extract inhibited the release of all cytokines except IL-1β, which slightly increased in comparison to the LPS control. All the tested compounds suppressed the production of IL-2, GM-CSF, and TNF-α. Whereas compounds 1, 2, 4-8, 10-15, 17, and 18 decreased production of IL-6, compounds 1, 2, 4, 7, 10, 13-15, and 17 inhibited the release of IL-1β. It is worth noting that most of the compounds tested showed a superior reduction in cytokines release compared to the reference drug ibuprofen.

Bioactive constituents of Lobostemon fruticosus: Anti-inflammatory properties and quantitative analysis of samples from different places in South Africa

Lobostemon fruticosus is South Africa medicinal plant traditionally used in treatment of wounds and skin diseases. Nevertheless, there is no report on its phytochemical constituents. LC–LTQ-Orbitrap mass spectrometry was used for identification and quantification of its constituents. A total of 13 compounds were identified from the leaves and twigs of the plant using NMR, ESI-HRMS and reference substances. The identified compounds were p-hydroxybenzoic acid (1), lycopsamine-N-oxide (2), caffeic acid (3), loliolide (4), 3-indolcarbaldehyde (5), globoidnan B (6), rabdosiin (7), syringaresinol (8), pinoresinol (9), rutin (10), rosmarinic acid (11), keampferol-3-O-rutinoside (12) and globoidnan A (13). In addition, quantitative determination of 6 marker compounds in samples from 12 different locations in South Africa was established. Rosmarinic acid and globoidnan A were found in large amount in the leaves and flowers of the plant. Samples from West Cape contained relatively greater amount of the tested compounds per dry weight than the other samples. The anti-inflammatory activities of isolated compounds were assessed by measuring the levels of cytokines IL-1β, IL-2, IL-6, GM-CSF and TNF-α in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS). At a concentration of 100 μM, compounds 7, 8 and 11 significantly decreased secretion of IL-1β, IL-2 and IL-6 compared to the LPS treated control (0.76–57.6%). All compounds significantly reduced the production of TNF-alpha compared to the LPS treated control (0.17–12.2%) and reference drug ibuprofen.

Development and Assessment of Lipidic Nanoemulsions Containing Sodium Hyaluronate and Indomethacin.

The present work attempts to develop and optimize the formula of a lipidic nanoemulsion (NE) containing sodium hyaluronate (HNa) and indomethacin (Ind) as HNa-Ind for enhanced transdermal antiarthritic activity. NEs were prepared by the spontaneous emulsification method and characterized by Fourier-transform infrared (FTIR) spectroscopy. The composition of the optimal formulation was statistically optimized using Box-Behnken experimental design method with three independent factors and was characterized for particle size, polydispersity index, and percent transmittance. The selected formula was tested for its in vitro antioxidant activity and in vivo anti-inflammatory activity. The optimized HNa-Ind NE formula was characterized and displayed a particle size of 12.87 ± 0.032 nm, polydispersity index of 0.606 ± 0.082, and 99.4 ± 0.1 percentage of transmittance. FTIR showed no interaction between HNa and Ind as a physical mixture. In addition, the optimized HNa-Ind NE was able to preserve the antioxidant ability of the two drugs, as evidenced through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition assay used to assess free radical scavenging ability. The cell viability was increased while the free radical scavenging activity was decreased (94.28% inhibition at higher concentrations compared with vitamin C as a reference with an inhibition of 100%). Moreover, the pharmacological anti-inflammatory potential of the optimized HNa-Ind NE formulation was assessed using an in vivo model. Compared with reference drugs (ibuprofen gel 5%), the remarkable activity of the optimized formulation was established using xylene-induced ear edema in mice model, in which the inflamed region reduced by 92.5% upon treatment. The optimized HNa-Ind NE formulation showed considerably higher skin permeation and drug deposition capability compared with the HNa-Ind solution. HNa-Ind NE was demonstrated to be a successful carrier with enhanced antioxidant and anti-inflammatory potential while showing better skin penetration, thus being a promising vehicle for transdermal drug delivery.

Synthesis and biological evaluation of ursolic acid derivatives containing an aminoguanidine moiety

Three series of ursolic acid derivatives containing an aminoguanidine moiety were designed, synthesized, and evaluated for anti-bacterial and anti-inflammatory activity. Some compounds displayed potent anti-bacterial activity against Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains, with minimum inhibitory concentration (MIC) values in the range of 2–64 µg/mL. Compounds 3a, 5a, and 7l showed significant inhibitory activity against the Gram-positive bacterial strain Staphylococcus aureus RN 4220, the Gram-negative bacterial strain Escherichia coli 1924, and four multidrug-resistant Gram-positive bacterial strains, with MIC values of 2 and 4 µg/mL. In anti-inflammatory tests, most of the compounds exhibited potent activity, in particular compound 3a displayed the most potent activity with 81.61% inhibition after intraperitoneal administration, which was more potent than ursolic acid and the reference drugs (ibuprofen and indomethacin). The cytotoxic activity of compound 3a was assessed in HeLa, Hep3B, and A549 cells.

Synthesis approach and biological activity evaluation of a series of 1,3,2-oxazaphosphole-2-oxides against inflammation and nociception

In the present work, we synthesized a series of substituted benzoxazaphosphole-2-oxides in high yields (68–84%). The approach involved the preparation of oxazaphospholo-2-oxide monochloride, which is the key substrate, followed by its treatment with amino-, hydroxyl-, and thiolocompounds under mild conditions to afford the corresponding cyclophosphamide, cyclophosphamidate, and cyclophosphathioamidate groups as target products. Lipophilicity prediction and in vivo antinociceptive and antiinflammatory properties of new molecules were determined. Out of 14 tested compounds, the most hydrophobic compounds were found to be also of the highest antinociceptive and the antiinflammatory effects compared with reference drugs ibuprofen and indomethacin. The pharmacological results also showed that three candidates from the cyclophosphamide group are more active as antiinflammatory agents than the reference drug at all the successive time intervals.

The preclinical study of a new nasal spray with the anti-inflammatory properties: the effect on the leukotriene-induced inflammation

The use of medicines of the local action with complex effects on the pathogenic cascade of acute rhinosinusitis (ARS) is expedient. Farmak Joint-Stock Company (Ukraine) has developed a new original dosage form of a nasal spray, which contains an aqueous solution of the known pharmaceutical substance Enisamium Iodide (EI). The presence of the effect on the leukotriene link inflammation in EI can determine the high rate of the antiexudative action development in the topical (intranasal) application. This may be useful for pathogenetic therapy of ARS on the background of acute respiratory viral infections taking into account the potential effectiveness for nasal congestion relief. Aim. To substantiate experimentally the expediency of application of a new nasal spray with EI under conditions of leukotriene-induced exudative inflammation. Materials and methods . A new nasal spray EI (JSC Farmak (Ukraine)) – “Amizon” – with the active substance concentration of 10 mg/ml was chosen as the study object. Ibuprofen – “Nurofen” (Reckitt Benckiser Helchere International Limited (UK)), film-coated tablets, 200 mg – was used as the reference drug and was administered once daily in the dose of 48 mg/kg intragastrically. The study of anti-inflammatory properties of EI (nasal spray, 10 mg/ml) in the external (epicutaneous) application was performed on white nonlinear rats of both genders in the experimental zymosan-induced inflammation development. The anti-inflammatory activity (AIA) of EI (nasal spray, 10 mg/ml) compared to Ibuprofen was assessed in percentage in dynamics in 0.5, 1 and 2 hours of observation. Results. According to the results of the studies conducted EI in the dosage form of a nasal spray in the active substance concentration of 10 mg/ml on the model of zymosan-induced inflammation of the rat foot showed the anti-inflammatory properties. According to the degree of its anti-inflammatory properties EI was not inferior to the reference drug Ibuprofen, but even exceeded its activity as of the 30 th minute of observation after zymosan injection. The result obtained allows suggesting the presence of high rate of the antiexudative action in the experimental object in the topical (intranasal) application in the treatment of patients with ARS due to the ability to inhibit the lipoxygenase route of the arachidonic acid metabolism. Conclusions . The presence of the anti-inflammatory activity of Enisamium Iodide (nasal spray) has been proven under conditions of leukotriene-induced inflammation reproduction on the model of the zymosan edema. By expression of the anti-inflammatory action during all periods of observation EI is not inferior to the reference drug Ibuprofen, exceeding the activity of the classical NSAID by 1.5 times as of the 30 th minute after the pathology onset. The anti-inflammatory activity of Enisamium Iodide in the dosage form of nasal spray experimentally substantiates the expediency and perspectivity of its further preclinical studies.

Methanolic Extract of Peel of Citrus maxima Fruits Exhibit Analgesic, CNS Depressant and Anti-inflammatory Activities in Swiss Albino Mice

Objectives: This study investigates analgesic, CNS depressant and anti-inflammatory activities of crude methanolic extract of Peel of Citrus maxima fruits. Materials and Methods: Methanolic extracts of Citrus maxima peel with different concentration were tested for analgesic activity in mouse model of acetic acid induced writhing and formalin induced licking and biting. Anti-inflammatory effect was tested by carrageenan induced paw edema model and the CNS depressant activity was evaluated by observing the reduction of locomotors activity by hole cross and open field test. Results: The extract, at 500 mg/kg, showed higher analgesic activity (73.34%) against acetic acid induced pain in mice while the standard reference drug Diclofenac sodium exhibited 87.13% activity at 10 mg/kg dose. The test dose at 500 mg/kg produced 48.23% protection in formalin induced hind paw licking and biting compared to 54.11% protection by the reference drug (10 mg/kg Diclofenac sodium). The antiinflammatory effect of the extract was comparable to reference drug Ibuprofen and the effect was sustained for 2-4 hr. However, the extract also showed significant dose dependent CNS depressant activity. Conclusion: Methanolic extract of peel of Citrus maxima fruits has CNS depressant effect with moderate analgesic and anti-inflammatory properties.

Synthesis, Characterization and Preliminary Pharmacological Evaluation of Triazolothiadiazoles Derived from some NSAIDs and Thiocarbohydrazide

The synthesis of new NSAIDs with improved efficacy and selectivity towards COX2, which encouraged by the various biological activities of 1,2,4-triazoles and 1,3,4-thiadiazoles. In this experiment, the production of 1,2,4-triazolothiadiazoles derivatives from Ibuprofen, Naproxen and Indomethacin. We have enhanced anti-inflammatory and analgesic activities by conventional method and microwave-assisted technique, and then compare the time consuming by reaction and yield percent of the product in both way, besides evaluation of anti-inflammatory action of the target compounds by pharmacological test with predictable selectivity towards COX-2 enzyme. Synthesis of the target compounds (P1a-3b, N1a-3b and I1a-3b) has been successfully accomplished by checking purity, characterization, also identification of the synthetic compounds which detected by estimation of physical properties, FT-IR and ¹H-NMR spectroscopy. In vivo potent anti-inflammatory activity of the ending compounds is evaluating in rats utilizing egg-white prompted edema model of inflammation. The experienced compounds (P1a-3b, N1a-3b and I1a-3b) and the reference drugs (Ibuprofen, Naproxen and Indomethacin) produced significant reduction in paw edema in compare to the effect of control group. Wholly tested compounds produced considerable decrease of paw edema in contrast to control group. However, compounds (P3b, N3b and I1b) have considerable more paw edema declining than Ibuprofen, Naproxen and Indomethacin. Intermediate and target compounds are synthesis by microwave method have better result by time and yield in compare with conventional way. The synthesized compounds (Pa1-3b and N1a-3b) may exhibit expected selectivity towards COX-2 enzyme properly due to their large size than its parent Ibuprofen, Naproxen.

Synthesis, Characterization and Preliminary Pharmacological Evaluation of Triazolothiadiazoles Derived from some NSAIDs and Thiocarbohydrazide

The synthesis of new NSAIDs with improved efficacy and selectivity towards COX2, which encouraged by the various biological activities of 1,2,4-triazoles and 1,3,4-thiadiazoles. In this experiment, the production of 1,2,4-triazolothiadiazoles derivatives from Ibuprofen, Naproxen and Indomethacin. We have enhanced anti-inflammatory and analgesic activities by conventional method and microwave-assisted technique, and then compare the time consuming by reaction and yield percent of the product in both way, besides evaluation of anti-inflammatory action of the target compounds by pharmacological test with predictable selectivity towards COX-2 enzyme. Synthesis of the target compounds (P1a-3b, N1a-3b and I1a-3b) has been successfully accomplished by checking purity, characterization, also identification of the synthetic compounds which detected by estimation of physical properties, FT-IR and ¹H-NMR spectroscopy. In vivo potent anti-inflammatory activity of the ending compounds are evaluating in rats utilizing egg-white prompted edema model of inflammation. The experienced compounds (P1a-3b, N1a-3b and I1a-3b) and the reference drugs (Ibuprofen, Naproxen and Indomethacin) produced significant reduction in paw edema in compare to the effect of control group. Wholly tested compounds produced considerable decrease of paw edema in contrast to control group. However, compounds (P3b, N3b and I1b) have considerable more paw edema declining than Ibuprofen, Naproxen and Indomethacin. Intermediate and target compounds are synthesis by microwave method have better result by time and yield in compare with conventional way. The synthesized compounds (Pa1-3b and N1a-3b) may exhibit expected selectivity towards COX-2 enzyme properly due to their large size than its parent Ibuprofen, Naproxen

Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents

Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, and HRMS. Most of the synthesized compounds showed pronounced anti-inflammatory effects at 100 mg/kg. In particular, compound 11b, which displayed the most potent anti-inflammatory activity of all of the compounds prepared, with 69.76% inhibition after intraperitoneal administration, was more potent than the reference drugs indomethacin and ibuprofen. The cytotoxicity of the compounds was also assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC50 >100 μmol/L). Furthermore, molecular docking studies of the synthesized compounds were performed to rationalize the obtained biological results. Overall, the results indicate that compound 11b could be a therapeutic candidate for the treatment of inflammation.

The study of the dose-dependent antiexudative effect of a new anti-inflammatory nasal spray

It is possible to assume that intranasal forms of drugs with the anti-inflammatory effect (AIE) can be effective for the pathogenic therapy of acute rhinosinusitis (ARS) to relieve nasal congestion.Aim. To determine AIE of Enisamium iodide (EI), assess the dose dependence of the effect, and substantiate the choice of the concentration for the active substance of EI in the form of a nasal spray for external use.Materials and methods. Enisamium iodide nasal spray – “Amizon” manufactured by JSC Farmak (Ukraine) was used in different concentrations extracutaneously. As a reference drug Ibuprofen – “Nurofen”, film-coated tablets, 200 mg, was used intragastrically in the dose of 48 mg/kg. The primary screening for the study of EI antiexudative action in three concentrations was conducted on the carrageenan-induced acute inflammatory model in rats. The anti-inflammatory activity (AIA) of EI in the concentrations of 5, 10 and 20 mg/ml was assessed in three hours compared to Ibuprofen. Results. EI in all studied concentrations had a statistically significant anti-inflammatory activity of various degrees with a non-linear character in the route of administration studied and the concentration range selected. Therefore, the choice of the most optimal concentration of EI (nasal spray) was on the basis of the comparative analysis of AIA of the drug test samples studied. The most pronounced AIA (35.3 %) was in the EI concentration of 10 mg/ml. This concentration is recommended for further preclinical studies. Conclusions. The study of AIA of Enisanium iodide (nasal spray) in the range of concentrations of 5, 10 and 20 mg/ml has shown the “activity-concentration” non-linear dependence. The most pronounced AIA is in the EI concentration of 10 mg/ml. Enisamium iodide (nasal spray) is a promising drug for further preclinical studies.

Total phenolic, flavonoid contents and in-vitro anti-inflammation evaluation of ethanol extracts of Hibiscus sabdariffa calyx, Malus domestica and their 1:1 extracts blend on protein denaturation

Abstract: Hibiscus sabdarifa and Malus domestica are well known and widely used herbs, which contains several interesting bioactive constituents and possesses health promoting properties. The aim of this study is to determine the total phenolic and flavonoid contents, evaluate and compare the anti-inflammatory effects of ethanol extracts of the two extracts and a 1:1 blend of the extracts against the denaturation of proteins in vitro. The respective extracts were analyzed for their contents of polyphenols and flavonoids. The test extracts and reference drug ( Ibuprofen ) of varying concentrations were also incubated with egg albumin under controlled experimental conditions and subjected to determination of absorbance to assess the anti-inflammatory property. The results obtained exhibited a concentration-dependent inhibition of protein denaturation by both extracts, the 1:1 blend as well as the reference drug. The EC 50 for extracts as well as those for the blend and the reference drug were determined by the dose-response curve using Graphpad Prism 5.0 software.