Carrageenan-induced Rat Paw Edema Assay Research Articles

Calotropis procera (Aiton) seeds fixed oil: Physicochemical analysis, GC–MS profiling and evaluation of its in-vivo anti-inflammatory and in-vitro antiparasitic activities

Calotropis procera (Aiton) is a wildly grown shrubbery that has been used by traditional healers in various remedies for centuries. Its different organs are reported to possess a variety of biological activities. However, a few reports chemically investigated the seed fixed oil, but they didn’t prospect its bioactivity. Accordingly, this study aimed to investigate the phytochemical composition, physicochemical properties, and biological activity of the seed oil. As well, exploration of the best extraction method that give the highest oil yield with the best composition. Physicochemical properties, total phenolic content and oxidative stability index of the oil were estimated. GC–MS analysis identified the oil content. Anti- inflammatory activity was examined using a carrageenan-induced rat paw edema assay. Immunomodulatory activity was determined by measuring the pro-inflammatory cytokines levels. Moreover, In- vitro anti-parasitic and antioxidant activities were studied. Soxhlet extraction method gives the highest yield of 40.5 ± 0.76% with no time interval. The oil shows a physicochemical property within the AOCS standards and low phenol content. GC-MS analysis reveals unsaturated fatty acids account for 75.25% of the oil, with an abundance of oleic acid (33.64%) and linoleic acid (31.95%). The oil exhibited potent anti-inflammatory and immunomodulatory activity. At various dose levels, paw edoema volume, pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) serum levels were reduced. The seed oil is a promising candidate for the treatment of inflammation and/or inflammatory associated diseases (as parasitic infections) besides its immunomodulatory activity.

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases.

The goal of achieving anti-inflammatory efficacy with the fewest possible adverse effects through selective COX-2 inhibition is still being investigated in order to develop drugs with safe profiles. This work shows the efficacy and safety profile of two novel benzimidazole piperidine and phenoxy pyridine derivatives in reaching this goal, which would be considered a major achievement in inflammatory therapy. The compounds were evaluated by virtual screening campaign, in vitro cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibition, in vivo carrageenan-induced rat paw edema assay, cytotoxicity against Raw264.7 cells, and histopathological examination of rat paw and stomach. Two new compounds, compound 1 ([(2-{[3-(4-methyl-1H-benzimidazol-2-yl)piperidin-1-yl]carbonyl}phenyl)amino]acetic acid) and compound 2 (ethyl 1-(5-cyano-2-hydroxyphenyl)-4-oxo-5-phenoxy-1,4-dihydropyridine-3-carboxylate) showed high selectivity against COX-2, favourable drug-likeness and ADME descriptors, a lack of cytotoxicity, relived paw edema, and inflammation without noticeable side effects on the stomach. These two compounds are promising new NSAIDs.

Bioactivities, physicochemical parameters and GC/MS profiling of the fixed oil of Cucumis melo L seeds: A focus on anti-inflammatory, immunomodulatory, and antimicrobial activities

Introduction: Recently, the recovery of waste products from plants as a source of biologically active compounds has increased interest. Therefore, the current research aims to evaluate the anti-inflammatory, immunomodulatory and antimicrobial activities of the fixed oil of Cucumis melo L seeds, as well as to investigate its physicochemical parameters and chemical composition. Methods: Anti-inflammatory activity was examined using carrageenan-induced rat paw edema assay. The antimicrobial activity was assayed against Staphylococcus aureus, Micrococcus luteus, Enterococcus faecalis, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans by well diffusion method. The chemical composition of the oil was determined by gas chromatography/mass spectrometry (GC/MS), α-tocopherol was estimated by high-performance liquid chromatography (HPLC). Results: Cucumis melo oil had no toxicity and possessed a promising anti-inflammatory activity. Moreover, the oil exhibited a reasonable decrease in the pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and a significant increase in the anti-inflammatory cytokine (IL-10). The oil exhibited a reasonable antimicrobial activity against all tested organisms. The major identified compound in the unsaponifiable matter was (1-methyldodecyl) benzene (8.76%), while the major fatty acid was methyl linoleate (14.10%). The results of physicochemical characterization revealed the better quality of Cucumis melo oil. The amount of α-tocopherol in the oil was 23.5 μg/mL, which is considered a reasonable amount. Conclusion: These findings indicate that the fixed oil of Cucumis melo L seeds might be used as a safe natural anti-inflammatory, immunomodulatory and antimicrobial agent.

Pharmacological Evaluation of Antipyretic, Analgesic and Anti-inflammatory Activities of Ethanolic Extract of Cassia fistula

Background: The antipyretic, analgesic and anti-inflammatory activities of two concentrations (100 and 200 mg/kg) of ethanolic extract of leaf, bark, flower and fruit pulp of C. fistula were determined in male wistar albino rats. Methods: Antipyretic activity was assessed by E. coli endotoxin induced pyrexia. Analgesic activity was assessed by hot plate, tail immersion and acetic acid induced writhing test. Anti-inflammatory activity was evaluated by carrageenan-induced rat paw edema assay. Result: Significant (p less than 0.05) antipyretic activity was exhibited from 2h onwards by bark extract @ 200 mg/kg and from 3h onwards by bark extract @100 mg/kg and leaves extract @ 200mg/kg as compared to control group. Significant (p less than 0.05) analgesic activity was shown by extract of bark @ 200 mg/kg as it is evident by increase in reflex time in hot plate (90,120,180 min), tail immersion test (120,180 min) and inhibition of writhing (32.12%). Significant (p less than 0.05) anti-inflammatory activity was exhibited from 3h post administration by bark @ 200 and leaves @ 100 and 200 mg/kg.

Synthesis, the antiexudative and antimicrobial activity of 6-arylidene substituted imidazo[2,1-b]thiazoles

Aim. To expand the range of 6-arylidene-2-methyl-2,3-dihydroimidazo[2,1-b]thiazolones as potential objects for studying the antiexudative and antimicrobial activities. Results and discussion. It has been shown that the condensation of synthetically affordable 2-methyl-2,3-dihydroimidazo[2,1-b]thiazolone with aromatic aldehydes can be successfully used for obtaining the corresponding 6-ylidene-functionalized derivatives. The biological screening of the compounds synthesized revealed that they possessed a low or moderate anti-inflammatory activity and inhibited the inflammation process in the range from 3 to 44 %. During the study of the antimicrobial activity of the substances obtained it was determined that their minimum bacteriostatic and minimum fungistatic concentrations ranged from 31.25 to 250 μg/mL. Experimental part. The interaction of 2-methyl-2,3-dihydroimidazo[2,1-b]thiazolone with a series of benzaldehydes and salicylic aldehydes in refluxing acetic acid in the presence of anhydrous sodium acetate leads to new 6-arylidene-2-methyl-2,3-dihydroimidazo[2,1-b]thiazolones. The antiexudative activity screening was performed on the model of carrageenan-induced paw oedema of white outbred male rats. The antimicrobial activity of the compounds was studied using the microtechnique of two-fold serial dilutions in a liquid nutrient medium. Conclusions. It has been found that the Knoevenagel condensation of 2-methyl-2,3-dihydroimidazo[2,1-b]thiazolone with aromatic aldehydes is a convenient way for the structural modification of the position 6 of the heterocyclic system by the arylidene moiety. The arylidene derivatives obtained show a moderate antiexudative activity in the carrageenan-induced rat paw oedema assay, as well as the antimicrobial activity against some gram-positive and gram-negative bacteria and fungi.

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

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

Synthesis, pharmacological evaluation and molecular docking of novel R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid as dual anti-inflammatory anti-platelet aggregation agents.

R-/S-2-(2-hydroxypropanamido) benzoic acid (R-/S-HPABA), marine-derived anti-inflammatory antiplatelet drugs, were initially synthesised in our group. However, preliminary research showed that R-/S-HPABA were eliminated rapidly because of extensive hydroxylation metabolism of phenyl ring in vivo. In order to reduce significant hydroxylation metabolism to improve pharmacological activity and bioavailability, trifluoromethyl group was incorporated into R-/S-HPABA to synthesise R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid (R-/S-HFBA), respectively. The purposes of this study were to report the synthesis of R-/S-HFBA and compare the anti-inflammatory antiplatelet effect and pharmacokinetic properties of R-/S-HFBA with those of R-/S-HPABA. Carrageenan-induced rat paw edema assay was used for the evaluation of the anti-inflammatory activity. R-/S-HFBA showed better results in inhibiting edema and were able to prolong the anti-inflammatory effect after carrageenan injection. The antiplatelet aggregation activity of R-/S-HFBA and R-/S-HPABA was studied on arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. The aggregation inhibition rate of R-/S-HFBA was significantly (p < 0.05) higher than that of R-/S-HPABA, respectively. Molecular docking study revealed that R-/S-HFBA possess more potent binding affinity with COX-1/COX-2 than R-/S-HPABA, respectively, and that the presence of trifluoromethyl group leads to increase in activity of R-/S-HFBA. R-/S-HFBA also afford more favorable pharmacokinetic properties than R-/S-HPABA, respectively, such as higher Cmax, larger AUC0-∞, and longer t1/2, which, as expected, are more metabolically stable.

Enzymatic synthesis of fatty acid esters of trehalose: Process optimization, characterization of the esters and evaluation of their bioactivities.

One-pot synthesis of caprylic, lauric and palmitic acid mono- and diesters of trehalose was catalyzed by the lipase Fermase CALB™ 10000. An optimized molar conversion of 35% of trehalose to its palmitate esters was obtained in acetone at 60°C with a trehalose:palmitic acid molar ratio of 1:5 in 4h. Trehalose fatty acid esters (THFAE) were purified by column chromatography and characterized using TLC, HPTLC, HR-MS, ATR-FTIR, and differential scanning calorimetry. THFAE were studied for their antimicrobial potential against four bacterial, and two fungal species. Trehalose monolaurate and trehalose dicaprylate demonstrated MIC of 0.45mM and 16mM against Pseudomonas aeruginosa and Escherichia coli, respectively. Trehalose monocaprylate showed the highest inhibition of biofilm forming property against Staphylococcus aureus (86.25%) at 99.2mM and trehalose dipalmitate had lowest IC50 of 13.23mM. Furthermore, their anti-inflammatory property was studied in vitro using 15-LOX inhibition assay and human red blood cell membrane stabilization assay. In the confirmatory in vivo tests using carrageenan-induced rat paw edema assay, inflammation in disease control group reached up to 63% as against 32% and 20% for trehalose dilaurate and diclofenac treated groups, respectively. THFAE can hence find potential applications in pharmaceuticals, functional foods, and nutraceuticals.

Anti-Inflammatory, Antipyretic and Analgesic Potential of Zilla spinosa in Animal Model

The anti-inflammatory, antipyretic and analgesic activities of two concentrations (250 and 500 mg/kg) of the chloroform and butanol fractions of Zilla spinosa were determined. The carrageenan-induced rat paw edema assay was exercised for assessing the anti-inflammatory activity in rats, yeast-induced hyperthermia was utilized to assess the antipyretic activity in mice and the analgesic activity was measured by three different methods (hot-plate test model in mice, tail flick test in mice and acetic acid-induced writhing in mice). The antioxidant activity was studied by using the DPPH assay. The chloroform fraction of the methanol extract of Z. spinosa (ZSC) demonstrated the maximum inhibition of inflammation (50% at 500 mg/kg; 44% at 250 mg/kg). The chloroform fraction showed significant antipyretic activities (p andlt; 0.001 at 500 mg/kg) after 60 and 120 min of administration. ZSC also exhibited significant analgesic activity (p andlt;0.001). The butanol fraction (ZSB) was inactive in all the biological screening assays.

Evaluation of anti-nociceptive, anti-inflammatory and antipyretic potential of Mikania cordata (Burm. f.) Robinson in experimental animal model

Mikania cordata is widely used for the treatment of cuts, wounds, and dengue fever in Bangladesh. In the present study, essential oil (12.5, 25 and 50 mg/kg) and two extracts, viz., chloroform and ethyl acetate extracts (200, 400, 800 mg/kg b.w.) were tested for peripheral and central anti-nociceptive activity by acetic acid-induced writhing and hot plate method, respectively. Carrageenan-induced rat paw edema assay and yeast-induced hyperthermia assay were also carried out to evaluate anti-inflammatory and antipyretic properties of oil and extracts, respectively at aforesaid doses. The essential oil (50 mg/kg), chloroform extract (800 mg/kg) and ethyl acetate extract (800 mg/kg) showed potent peripheral anti-nociceptive activity having 47.33%, 29.33% and 16.65% of writhing inhibition, respectively, comparable with standard diclofenac (52.0%). Essential oil (50 mg/kg), chloroform extract (800 mg/kg) and ethyl acetate extract (800 mg/kg) presented promising central anti-nociceptive activity as well having 95.86%, 79.18% and 42.37% elongation of reaction time, respectively, at 90 min after administration of essential oil, ethyl acetate extract and 60 min after administration of chloroform extract. In anti-inflammatory activity screening, the essential oil (50 mg/kg) produced the highest 72.80% edema inhibition at 4 h after administration of carrageenan which was comparable with that of standard phenylbutazoe (87.87%). On the other hand, chloroform extract (800 mg/kg) and ethyl acetate extract (800 mg/kg) showed up to 34.31% and 15.27% of edema inhibition, respectively, at 4 h after administration of carrageenan. In antipyretic assay, the essential oil and chloroform extract displayed a strong antipyretic effect in yeast-induced rats, whereas the ethyl acetate extract had no antipyretic activity. The present study revealed anti-nociceptive, anti-inflammatory and antipyretic potential of M. cordata which could be the therapeutic option against fever, inflammations as well as painful conditions and confirmed the traditional use of M. cordata.

A simple and efficient one-pot novel synthesis of pyrazolo[3,4-b][1,8]naphthyridine and pyrazolo[3,4-d]pyrimido[1,2-a]pyrimidine derivatives as anti-inflammatory agents

An efficient one-pot synthesis of novel pyrazolo[3,4-b][1,8]naphthyridine and pyrazolo[3,4-d]pyrimido[1,2-a]pyrimidine derivatives has been investigated from the reaction of 2-amino (pyrimidine or pyridine), aromatic aldehydes and 3-methyl-1-phenyl-2-pyrazolin-5-one. All synthesized compounds were evaluated for in vivo anti-inflammatory activity using carrageenan-induced rat paw edema assay. Compounds 4a, 4e, 4g, 5a, 5b (80%) and 5c (86%) showed good to excellent results when compared with the anti-inflammatory active standard drug diclofenac Na (93%). On the basis of the structure–activity relationship, the anti-inflammatory activity of pyrazolo[3,4-d]pyrimido[1,2-a]pyrimidine derivatives has been found to be much better than pyrazolo[3,4-b][1,8]naphthyridine derivatives.

Synthesis, biological evaluation, molecular docking, and ADMET studies of some isoxazole-based amides

Some isoxazole-based amides were synthesized by the reaction of 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride with various aliphatic, aromatic and heterocyclic amines; characterized by analysis of spectroscopic data and evaluated for in vivo anti-inflammatory, ulcerogenic, and antimicrobial activity. Compounds A1, A7, and A10 were identified as the potent anti-inflammatory agents in carrageenan-induced albino rat paw edema assay exhibiting 92.85–93.57% edema inhibition after 5 h with lower ulcer index (2.5) than the standard diclofinac sodium (6.15). Antibacterial activity against the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was found to be good in comparison with the standard ampicillin in terms of minimum inhibitory concentration values. Anti-inflammatory activity results were supported by molecular docking—possible binding modes, interactions, and docking scores of titled compounds with the active site of cyclooxygenase-2 enzyme. In silico absorption, distribution, metabolism, and excretion–toxicity study was also performed to predict the preliminary pharmacological, pharmacokinetic, and toxicity profile of the synthesized anti-inflammatory agents suggesting that these derivatives have good oral drug like behavior and non-toxic nature.

Pyrazole-hydrazone derivatives as anti-inflammatory agents: Design, synthesis, biological evaluation, COX-1,2/5-LOX inhibition and docking study

A new series of pyrazole-hydrazone derivatives 4a-i were designed and synthesized, their chemical structures were confirmed by IR, 1H NMR, 13C NMR, MS spectral data and elemental analysis. IC50 values for all prepared compounds to inhibit COX-1, COX-2 and 5-LOX enzymes were determined in vitro. Compounds 4a (IC50=0.67μM) and 4b (IC50=0.58μM) showed better COX-2 inhibitory activity than celecoxib (IC50=0.87μM) with selectivity index (SI=8.41, 10.55 in sequent) relative to celecoxib (SI=8.85). Also, compound 4a and 4b exhibited superior inhibitory activity against 5-LOX (IC50=1.92, 2.31μM) higher than zileuton (IC50=2.43μM). All target pyrazoles were screened for their ability to reduce nitric oxide production in LPS stimulated peritoneal macrophages. Compounds 4a, 4b, 4f and 4i displayed concentration dependent reduction and were screened for in vivo anti-inflammatory activity using carrageenan-induced rat paw edema assay. Compound 4f showed the highest anti-inflammatory activity (% edema inhibition=15–20%) at all doses when compared to reference drug celecoxib (% edema inhibition=15.7–17.5%). Docking studies were carried out to investigate the interaction of target compounds with COX-2 enzyme active site.

Novel 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene analogues as selective COX-2 inhibitors: Design, synthesis, anti-inflammatory evaluation, and molecular docking studies

A series of 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene derivatives were synthesized and evaluated for in vitro COX inhibitory potential. Within the series, compounds 4a, 4j, 4k, and 4q were identified as potential and selective COX-2 inhibitors with COX-2 IC50 in 0.31–1.40µM range; COX-2 selectivity index (SI)=48.8–183.8 range and they showed percent PGE-2 inhibitory activity in the range of 25.4–46.9. Further, compounds 4a, 4j, 4k and 4q displayed potent anti-inflammatory activity with percentage rise in paw volume ranging from 21.1–30.5 at 180min, while celecoxib demonstrated 19.6 percentage rise at the same dose at 180min in carrageenan-induced rat paw edema assay. Cell viability via MTT assay showed no cytotoxicity up to 80µM concentrations. Molecular docking study of potent compounds in the series showed Gscore comparable to celecoxib with similar binding orientation for the COX-2 active site which also corroborates the observed in vitro COX-2 inhibition.

Synthesis, conformational assignment, and anti-inflammatory activities of N-arylidene-2-(4-chloro-2-(2-substituted phenoxy)phenyl)acetic acid hydrazides

A series of N-arylidene-2-(4-chloro-2-(2-fluoro or chlorophenoxy)phenyl)acetic acid hydrazides (16 or 17) was synthesized for their anti-inflammatory activity by the condensation of corresponding hydrazide and aromatic aldehydes. Characterization of these compounds by proton nuclear magnetic resonance showed most of the protons as two separate peaks. The energy was calculated for each possible configuration, and their stereochemical behavior was studied using proton nuclear magnetic resonance techniques. The results indicated that the most stable stereoisomers are the two E geometrical isomers, which undergo a rapid cis/trans amide equilibrium with the cis conformer predominating. These analogs exhibited moderate to excellent anti-inflammatory activity in carrageenan-induced rat paw edema assay. Among them, N-(3,4-dimethoxybenzylidene)-2-(4-chloro-2-(2-chlorophenoxy)phenyl)acetic acid hydrazide (17k) showed the highest anti-inflammatory activity relative to diclofenac sodium acid as a reference drug (86 % vs. 61 % reduction in inflammation post drug administration, respectively).

Nanoparticle formulation of 11-keto-β-boswellic acid (KBA): anti-inflammatory activity and in vivo pharmacokinetics

Context: The oleo-gum-resin of Boswellia serrata Roxb. (Burseraceae) is widely used for the treatment of inflammatory diseases such as osteoarthritis, rheumatoid arthritis and cancer. Anti-inflammatory activity of 11-keto-β-boswellic acid (KBA) is impeded by poor oral bioavailability due to its high lipid solubility, rapid phase-1 metabolism and poor intestinal permeability.Objective: This study developed a poly-dl-lactide-co-glycolide-based nanoparticle formulation of KBA to improve its oral bioavailability and in vivo anti-inflammatory activity.Materials and methods: KBA was isolated from the oleo-gum resin of B. serrata, and its nanoparticle formulation (KBA-NPs) was prepared by the emulsion–diffusion–evaporation method. Oral bioavailability of KBA and KBA-NPs was studied at 50 mg/kg p.o. dose in Sprague–Dawley rats, and further evaluated for in vivo anti-inflammatory activity in carrageenan-induced rat paw oedema assay at the same dose level.Results: The prepared KBA-NPs had a particle size of 152.6 nm with polydispersity index of 0.194, 79.7% entrapment efficiency and a cumulative 61.5% release of KBA from KBA-NPs, at 72 h. KBA-NPs showed 60.8% inhibition of rat paw oedema at 5 h as compared to 34.9% as that of KBA. The results of oral bioavailability study and in vivo anti-inflammatory activity showed 7- and 1.7-fold increase in bioavailability and anti-inflammatory activity, respectively, of KBA in KBA-NPs as compared to KBA alone.Conclusion: The results of improved oral bioavailability and in vivo anti-inflammatory activity of KBA-NPs suggested successful development of KBA nanoparticle formulation.

A convenient synthesis, reactions and biological studies of some novel selenolo[2,3-c]pyrazole compounds as antimicrobial and anti-inflammatory agents

5-Chloro-3-methyl-1-phenylpyrazole-4-carbonitrile 3 was reacted with selenium in the presence of sodium borohydride and chloroacetamide to afford selanyl acetamide 5, which underwent Thorpe–Ziegler cyclization upon heating with sodium ethoxide to give the novel synthesized 4-amino-3-methyl-1-phenyl-1H-selenolo[2,3-c]pyrazole-5-carboxamide compound (6). The latter compound was used as a versatile precursor for synthesis of other heterocyclic rings, namely pyrimidine, imidazopyrimidine and thiadiazinopyrimidine fused to selenolo[2,3-c]pyrazole moiety. The newly synthesized compounds and their derivatives were characterized by elemental and spectral analysis (IR, 1H NMR, 13C NMR and mass spectrometric analyses). Furthermore, some of these synthesized compounds were screened against various pathogenic bacterial and fungal strains. The results demonstrate that most of the synthesized compounds possess a significant antibacterial activity against gram-positive and gram-negative bacteria. Also, some of these compounds showed a remarkable antifungal activity, especially Candida albicans. On the other hand, some of the synthesized compounds possess high anti-inflammatory activity using carrageenan-induced rat paw edema assay compared with indomethacin. The present work discussed synthesis of new selenolo[2,3-c]pyrazoles fused to other heterocyclic rings, namely pyrimidine, imidazopyrimidine and thiadiazinopyrimidine. Some of the synthesized compounds showed remarkable antibacterial, antifungal and anti-inflammatory activities.

Synthesis, Structure Activity Relationship (SAR), and Biological Activities of Benzylideneacetophenones Derivatives

Oxygen has double-edge properties as it is essential for life, but can also provoke oxidative stress by protein & lipid per oxidation. The persistent oxidative stress and excess LPO induce several inflammatory mediators such as prostaglandins and leuckotrienes by activating enzymes cyclooxygenase and lipoxygenase. The per oxidation can be blocked by free radical scavengers as antiinflammatory agents. Most of the anti-inflammatory agents, which inhibit the above mentioned enzymes, are associated with side effects such as ulceration and bleeding in gastrointestinal tract; so the attention is focused on benzylideneacetophenones having antinflammatory, antioxidant and gastric protectant activities by virtue of free radical scavengers. A systematic analysis of the structural features responsible for biological activities and a possible mode of their actions were proposed to be evaluated by synthesizing a set of compounds, screening them for anti-inflammatory, antioxidant and antiulcer activity. The benzylideneacetophenones derivatives were synthesized employing the Claisen-Schmidt condensation. The structure of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory (carrageenan-induced rat paw edema assay), antioxidant (inhibition of lipid peroxidation) and antiulcer activity (indomethacin-induced gastric damage). Possible correlation between observed biological activities and substituents at different positions on rings was also studied. The data revealed that compounds 1e, 1m and 1l showed equivalent activity to indomethacin (reference drug) at the fourth hour at dose of 100 mg/kg. Among the tested compounds 1m & 1l exhibited the highest lipid per oxidation inhibitory activity (IC50 2.38µg/ml, 3.08 µg/ml) followed by 1i, 1h, 1e. In addition, all compounds at the tested dose level (100mg/kg, p.o.) exhibited varying degree of activity against ulceration induced by indomethacin. The compounds 1m, 1l, 1e, and 1i showed excellent activity (71-75%), whereas compounds 1d, 1h and 1j exhibited good to moderate (60-69%) activity. SAR analysis revealed that presence of electron donating groups on p- position of both rings A and B seems to enhance anti-inflammatory, antioxidant and antiulcer activity. The compound 1m (4-amino-4'-ethoxychalcone) and 1l (4-amino-4'-methoxychalcone) have equivalent antiinflammatory activity in comparison with the reference drug. Moreover, the same compounds also obtained promising antioxidant and antiulcer activities. Thus, I m could be explored further for development of potent anti inflammatory agent.

Synthesis, anti-inflammatory, ulcerogenic and cyclooxygenase activities of indenopyrimidine derivatives.

Objective of the present work was to evaluate the anti-inflammatory, ulcerogenicity and cyclooxygenase activity of indenopyrimidine derivatives. Anti-inflammatory activity of the tested compounds is investigated by carrageenan-induced rat paw edema assay. Compounds A1, A6, A7 and A12 exhibit the comparable anti-inflammatory activity (79.33-81.33%) to the standard drug diclofenac sodium (85.33%), while A6, A7, A9, A12 and A14 show better ulcer index than the reference standard diclofenac sodium. To rationalize the anti-inflammatory activity, docking experiments are performed to study the ability of these compounds to bind into the active site of COX-2 enzyme.

One-pot synthesis and in vivo biological evaluation of new pyrimidine privileged scaffolds as potent anti-inflammatory agents

A simple methodology has been developed for the synthesis of diverse members of multifunctionalized 4-hydroxy-2-methyl-6-(phenyl)pyrimidine-5-carbonitrile derivatives via multicomponent reaction of aromatic aldehydes, ethyl cyanoacetate, and acetamidine hydrochloride using a quantitative amount of NaOH in dry DMF at 80 °C in a single procedural step. The carbon skeleton of synthesized compounds resembles the bacimethrin, an antibiotic active against several yeast and bacteria. The anti-inflammatory activities of all the synthesized compounds were assessed on Wistar rats using diclofenac sodium as a standard reference. The compound AC1, 2, 5, 9, and AC10 showed promising anti-inflammatory activity (80–83 %) in comparison with diclofenac sodium (85 %) in the carrageenan-induced rat paw edema assay, which is the key finding of this article. The synthesized 4-hydroxy-2-methyl-6-(phenyl)pyrimidine-5-carbonitrile derivatives shown promising anti-inflammatory activity (80–83 %) in comparison with diclofenac sodium (85 %) in the carrageenan-induced rat paw edema assay.