Anti-inflammatory Analgesic Activity Research Articles

Formulation and Evaluation of Polyherbal Cream

Cosmetics made from either natural or synthetic components are almost in regular use universally in many different forms for enhancing the beauty. Azadirachta indica and Nyctanthes arbor-tristis are medicinal plants; these plants are used traditionally from ancient years in various herbal medicinal systems such as Ayurvedic, Homeopathic and Siddha. The dried leaves of Azadirachta indica and dried leaves of Nyctanthes arbor-tristis have antibacterial, anti-inflammatory analgesic activity. The present research is focused on the formulation of polyherbal cream and their evaluation by using various evaluation parameters.
 Keywords: Polyherbal cream, Neem, Night Jasmine, Fusion method, Almond oil.

FORMULATION AND EVALUATION OF POLYHERBAL CREAM

Objective: Eugenia caryophyllus, Zingiber officinale and Nyctanthes arbor-tristis are medicinal plants; these plants are used traditionally from ancient year in the various herbal medicinal system such as Ayurvedic, Homeopathic and Siddha. The clove buds of Eugenia caryophyllus, rhizomes of Zingiber officinale and dried leaves of Nyctanthes arbor-tristis have anti-inflammatory analgesic activity. The present research was focus on the formulation of polyherbal cream and their evaluation by using various evaluation parameters of the present research are to formulate polyherbal cream and to evaluate the polyherbal cream.
 Methods: the slab method was used for the preparation of cream.
 Results: The evaluation parameters are coming under this heading physical parameter like color was slightly white green, the odor was characteristics, consistency was smooth and the state was semisolid. PH of the cream was 6.5; Spreadability was 7.4g. cm/sec time required for this test was 15 sec, Washability was easily washable, the cream was nonirritant, viscosity of the formulated cream was 39010 cps and no phase separation was observed during storage of polyherbal cream.
 Conclusion: This cream formulation was used in rheumatoid arthritis to reduce joint pains. This cream formulation was o/w type of emulsion; hence this formulation was easily washed with plane water after application.

Screening of N-Benzoyl Isoserine Methyl Ester (N-bime) for anti-inflammatory analgesic activity and toxicity profile in animals

Background: Pain and inflammation are the basic processes involved in the pathogenesis of many diseases. Non-steroidal anti-inflammatory drugs are often used to treat rheumatic diseases. The study compound N-Benzoyl Isoserine Methyl Ester (N-bime) is a newly synthesized propionic acid derivative by National Chemical Laboratory, Pune. Since the biological data of this compound is not available, the present study has been planned to screen this compound for anti-inflammatory, analgesic activity and its toxicity profile in animals.Methods: Single dose toxicity study was carried out in rats. Anti-inflammatory activity was tested by Rat Hind Paw Oedema and Cotton Pellet Implantation method. For Analgesic activity, Acetic acid induced writhing and Tail Pinch method was used. Yeast induced Pyrexia was used for evaluation of anti-pyretic activity. Ibuprofen was the positive control. Data are presented as mean±SEM. Statistical analysis was performed by analysis of variance and students unpaired‘t’ test.Results: The test compound N-bime did not show any apparent adverse effects or mortality in the dose range 1mg - 500mg / 100gm body weight in animals. It showed better anti-inflammatory actions in higher doses as compared to Ibuprofen (p˂ 0.05). In acetic acid induced writhing test N-bime offered better protection against writhes, than Ibuprofen. But, both failed to demonstrate analgesic activity in the Tail Pinch method. N-bime showed a gradual decrease in temperature in the anti-pyretic test (P<0.001).Conclusions: The present study indicates that N-bime does possess anti-inflammatory, analgesic and weak anti-pyretic properties like the NSAIDs. It has proved to be safe in the dose range of 1mg - 500mg / 100gm body weight in rats and mice.

Design, synthesis and pharmacological evaluation of some pyrazolopyrimidin-6(7H)-ones and tricyclic 8-oxo-dihydrooxazolopyrazolopyrimidin-9-ium chloride derivatives

In the present study, some pyrazolopyrimidin-6(7H)-ones and tricyclic 8-oxo-dihydrooxazolopyrazolopyrimidin-9-ium chloride derivatives were synthesized and tested for anti-inflammatory and analgesic activity and assessment of acute ulcerogenic propensity as compared to the standard drug indomethacin. Some of the compounds (2c–2e; 3c–3e) showed appreciable anti-inflammatory–analgesic activity at the evaluated equimolar dose with lower ulcerogenic profile when compared with the standard. Compounds containing fused dihydrooxazolo ring (3e) system were found to be more active than their corresponding congener pyrazolopyrimidine.

A joint theoretical and experimental structural study of two novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine derivatives

In this study, two novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine derivatives, 3-[2-(4-methoxyphenyl)ethyl]-6-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine (compound 1) and 3-[2-(3,4,5-trimethoxyphenyl)ethyl]-6-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine (compound 2), having analgesic–anti-inflammatory activity were synthesized and characterized by IR, 1H-NMR, and mass spectroscopic techniques besides elementary analysis. Additionally, the structures and molecular packings of the mentioned compounds have been investigated by X-ray single crystal diffraction. The six-membered thiadiazine ring adopts the screw boat conformation in both the compounds. In the crystal packings of the compounds 1 and 2, C–H···N and C–H···O interactions link the molecules into a two-dimensional network and generate infinite chains. Furthermore, C–H···π intermolecular interactions provide further stability to the molecular packing in both the molecules. The conformers have been predicted by the potential energy surface scan employing the AM1 method. Geometry optimizations and electrostatic properties have been obtained using AM1 and ab initio quantum methods.

A new therapeutic approach in Alzheimer disease: Some novel pyrazole derivatives as dual MAO-B inhibitors and antiinflammatory analgesics

The increasing life expectancy in our population makes Alzheimer’s disease (AD) a growing public health problem. There is a great need to find a way to prevent and delay the disease. It was shown that monoamine oxidase-B (MAO-B) inhibitors and antiinflammatory agents might be effective in treating AD. Therefore, a novel series of 1-thiocarbamoyl-3-substituted phenyl-5-(2-pyrrolyl)-4,5-dihydro-(1 H)-pyrazole derivatives as promising MAO-B inhibitors was synthesized and investigated for the ability to inhibit selectively the activity of the A and B isoforms of monoamine oxidase (MAO). Most of the synthesized compounds showed high activity against both the MAO-A (compounds 3e– 3h) and the MAO-B (compounds 3i– 3l) isoforms. All the synthesized compounds were also tested for their in vivo antiinflammatory activity by two different bioassays namely, carrageenan-induced oedema and acetic acid-induced increase in capillary permeability in mice. In addition, analgesic and ulcerogenic activities were determined. The combined antiinflammatory data from in vivo animal models showed that compound 3k exhibited anti-inflammatory activity comparable to that of indomethacin with no ulcerogenic effects. Since compound 3k exhibits both antiinflammatory-analgesic activity and MAO-B inhibition, it needs further detailed studies.

Preparation of 5-aryl-3-alkylthio-l,2,4-triazoles and corresponding sulfones with antiinflammatory–analgesic activity

In this study, a series of 5-aryl-3-alkylthio-1,2,4-triazoles and corresponding sulfones were prepared with the objective of developing better analgesic–antiinflammatory compounds with minimum ulcerogenic risk. The structures of the compounds were elucidated by spectral and elemental analysis. The compounds were assayed per os in mice for their antiinflammatory and analgesic activity as well as the ulcerogenic risk and acute toxicity. Several of these compounds showed significant activity. Alkylsulfone derivatives were found to be much more potent analgesic–antiinflammatory agents than the corresponding alkylthio analogs. Compounds 9 and 11 were the most active of the series in both analgesic and antiinflammatory activity tests. In contrast to reference compound acetyl salicylic acid, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic/antiinflammatory activity.

Facile Synthesis of Multisubstituted Buta‐1,3‐dienes via Suzuki—Miyaura and Kumada Cross‐Coupling Strategy of 2,4‐Diiodo‐buta‐1‐enes with Arylboronic Acids and Grignard Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Facile synthesis of multisubstituted buta-1,3-dienes via Suzuki–Miyaura and Kumada cross-coupling strategy of 2,4-diiodo-buta-1-enes with arylboronic acids and Grignard reagents

One-pot Suzuki-Miyaura-type and Kumada-type cross-coupling reactions of 2,4-diiodo-buta-1-enes with arylboronic acids and alkyl/aryl magnesium bromides were carried out in the presence of accessibly simple catalysts under mild conditions. As a result, some 1,1,2-trisubstituted buta-1,3-dienes were obtained including the Tamoxifen-type, which have potential adjuvant therapy in women who have suffered from breast cancer and cyclooxygenase-2-type (COX-2-type) inhibitors, some of which have been proved to elicit efficient anti-inflammatory analgesic activities and less adverse gastrointestinal side effects and to be very useful in the prophylactic treatment of a wide variety of cancers and neurodegenerative disorders.

Synthesis and Analgesic‐Antiinflammatory Activities of Some 1,2,4‐Triazine Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Design, syntheses, and evaluation of 2,3‐diphenylcycloprop‐2‐en‐1‐ones and oxime derivatives as potential cyclooxygenase‐2 (COX‐2) inhibitors with analgesic‐antiinflammatory activity

AbstractA group of 2,3‐diphenylcycloprop‐2‐enes having a variety of substituents at the para‐position of the C‐2 phenyl ring (H, F), and C‐3 phenyl ring (H, F, SMe, SOMe, SO2Me), in conjunction with either a C‐1 carbonyl, oxime, oxime acetate, benzoyl hydrazone, or hydrogen substituent were synthesized for in vivo evaluation as analgesic and antiinflammatory (AI) agents, and as potential selective cyclooxygenase‐2 (COX‐2) inhibitors. This group of cycloprop‐2‐ene compounds exhibited significant analgesic activity, since 4% NaCl‐induced abdominal constriction was reduced by 43–90% at 30 min, and 41–100% at 60 min, after drug administration relative to the reference drugs aspirin and celecoxib (58% and 32% inhibition at 30 min after drug administration) for a 50 mg/kg intraperitoneal dose. AI activities, determined using the carrageenan‐induced rat paw edema assay, showed that this class of cycloprop‐2‐ene compounds exhibited AI activities in the inactive‐to‐modest activity range (0–26% inhibition) for a 50 mg/kg oral dose. The AI potency order for a group of 2,3‐diphenylcycloprop‐2‐enes with respect to the C‐1 substituent was oxime>hydrogen>carbonyl>benzoyl hydrazone. 2,3‐Diphenylcycloprop‐2‐en‐1‐one oxime (20) was the most active AI agent, inducing a 26% reduction in inflammation, relative to the reference drugs ibuprofen and celecoxib, which showed 52% and 58% reductions in inflammation, at 5 h after drug administration. In vitro COX‐1 and COX‐2 inhibition studies showed that 2,3‐diphenylcycloprop‐2‐en‐1‐one oxime (20) is a selective COX‐2 inhibitor (COX‐1 IC50>100 μM; COX‐2 IC50=2.94 μM; COX‐2 selectivity index>34). A molecular modeling study that docked the oxime (20) in the active site of the human COX‐2 isozyme showed that it binds in the vicinity of the mouth of the COX‐2 binding site with the O‐atom of the oxime (=N–OH) moiety separated from the NH2 group of Arg120 by about 3.65 Å. This orientation of the oxime compound (20) in the COX‐2 binding site could be due to a potentially strong ionic interaction between the =NOH oxime moiety and the guanidinium moiety of Arg120. Drug Dev. Res. 57:6–17, 2002. © 2002 Wiley‐Liss, Inc.

Design, syntheses, and evaluation of novel 1,1‐dihalo‐2,3‐diphenylcyclopropanes as potential cyclooxygenase‐2 (COX‐2) inhibitors with analgesic‐antiinflammatory activity

AbstractA group of (Z)‐ and (E)‐1,1‐dihalo‐2‐(4‐substituted‐phenyl)‐3‐phenylcyclopropane [(Z)‐10, (E)‐11] stereoisomers having a variety of substituents (H, Br, Cl, F, NO2, SO2Me) at the para‐position of the C‐2 phenyl ring in conjunction with either two chloro or bromo substituents at C‐1 were synthesized for in vivo evaluation as analgesic and antiinflammatory (AI) agents, and as potential selective cyclooxygenase‐2 (COX‐2) inhibitors. This group of compounds (10‐11) exhibited significant analgesic activity since 4% NaCl‐induced abdominal constriction was reduced by 44–73% at 30 min, and 48–77% at 60 min, post‐drug administration relative to the reference drugs aspirin and celecoxib (58 and 32% inhibition at 30 min post‐drug administration) for a 50 mg/kg intraperitoneal dose. In the 1,1‐dichloro group of compounds, a Cl or MeSO2 substituent at the para‐position of the C‐2 phenyl ring generally provided superior analgesic activity. The most active analgesic compound, (E)‐1,1‐dichloro‐2‐(4‐methanesufonylphenyl)‐3‐phenylcyclopropane (11h) inhibited abdominal constriction by 72 and 77% at 30 and 60 min post‐drug administration, respectively. AI activities, determined using the carrageenan‐induced rat paw edema assay, showed that this class of (Z)‐10 and (E)‐11 compounds exhibited AI activities in the inactive‐to‐moderate activity range (1.5–45% inhibition) for a 50 mg/kg oral dose. The AI potency order, with respect to the para‐substitutent on the C‐2 phenyl ring, for the (Z)‐10 compounds was NO2 > MeSO2 ≈ H ≥ Cl, and for the (E)‐11 compounds was H ≥ MeSO2 > Cl ≈ Br. (E)‐1,1‐dibromo‐2‐(4‐methanesufonylphenyl)‐3‐phenylcyclopropane (11l), which was the most active AI compound, reduced inflammation by 45 and 37% at 3 and 5 h post‐drug administration, respectively. The (E)‐11 stereoisomer was generally a more potent AI agent than the corresponding (Z)‐10 stereoisomer. In vitro COX‐1 and COX‐2 inhibition studies showed that (E)‐1,1‐dichloro‐2‐(4‐nitrophenyl)‐3‐phenylcyclopropane (11c) inhibited COX‐1 (IC50 = 278.8 μM) and COX‐2 (IC50 = 80.5 μM) for a COX‐2 selectivity index of 3.5, whereas (E)‐1,1‐dichloro‐2‐(4‐methanesulfonylphenyl)‐3‐phenylcyclopropane (11h) was a more potent inhibitor of COX‐1 and COX‐2, but it was more selective for COX‐1 (COX‐1 IC50 = 0.59 μM, COX‐2 IC50 = 3.04 μM). A molecular modeling (docking) study for (E)‐1,1‐dichloro‐2‐(4‐methanesulfonylphenyl)‐3‐phenylcyclopropane (11h) on the active site of the human COX‐2 isozyme shows it binds in the center of the active site with the 1,1‐dichloro substituents oriented in the direction of the mouth of the channel towards Arg120, and the C‐2 MeSO2 moiety oriented towards the apex of the active site with the S‐atom of the MeSO2 substituent positioned about 6.56 Å inside the entrance to the secondary pocket (Val523) of COX‐2. In contrast, the corresponding (Z)‐10h stereoisomer assumes a different position in the COX‐2 binding site where the S‐atom of the MeSO2 moiety is near (4.02 Å) the Ser530 OH, but a much greater distance from the COX‐2 secondary pocket (Val523). The results from these docking studies are consistent with the observation that (E)‐11h is an inhibitor of both COX isozymes, whereas the (Z)‐10h stereoisomer is an inactive COX inhibitor (COX‐1 IC50 > 100 μM, COX‐2 IC50 > 200 μM). Drug Dev. Res. 55:79–90, 2002. © 2002 Wiley‐Liss, Inc.

Synthesis and analgesic-antiinflammatory activities of novel acylarylhydrazones with a 5-phenyl-4-R-3-pyrrolyl-acyl moiety.

A new series of arylidene 5-phenyl-4-R-pyrrole-3-carbohydrazides 1a-j were prepared and evaluated for their analgesic-antiinflammatory activities. All synthesized compounds showed a significant analgesic action in mice after intraperitoneal administration at a dose of 100 microM/kg. Two of these, 1b, (4'-methylbenzylidene)-5-phenyl-1H-pyrrole-3-carbohydrazide, and 1d, (4'-chlorobenzylidene)-5-phenyl-1H-pyrrole-3-carbohydrazide, were found to be more potent as antinociceptive agents respect to dipyrone and indometacin, used as reference drugs. Among compounds 1, only 1b showed a moderate antiinflammatory effect in rats while 1d proved to be a potent non antiinflammatory analgesic.

Synthesis and analgesic-antiinflammatory activities of ethyl 2-[3-(1-phenoxy(methoxy)carbonyl-4-aryl-(alkyl)-1,4-dihydropyridyl)]acetates

Reaction of ethyl 2-(3-pyridyl)acetate 4a or ethyl 2-methyl-2-(3-pyridyl)acetate 4b, with phenyl chloroformate or methyl chloroform ate, afforded the intermediate pyridinium salt 5 which undergoes regioselective nucleophilic attack at C-4 upon reaction with a Grignard reagent in the presence of a cuprous iodide catalyst at −23° to yield the corresponding ethyl 2-[3-(1-phenoxy(methoxy)carbonyl-4-aryl(alkyl)-1,4-dihydropyridyl)]acetates 6a-f in 64–96% chemical yield. No product arising from reaction of the ester substituent of the pyridinium salt 5 with the Grignard reagent was observed. The 1H nmr spectra of 6a-f exhibited dual resonances for the 1,4-dihydropyridyl H-2, H-5 and H-6 protons at 25° in deuteriochloroform. These dual resonaces were attributed to two different rotameric configurations resulting from restricted rotation about the nitrogen-to-carbonyl carbamate bond due to its double bond character. Compound 6 generally exhibited superior analgesic and antiinflammatory activities, compared to the reference drugs aspirin and ibuprofen, respectively. These structure-activity correlations indicate the 1,4-dihydropyridyl ring system present in 6 is a suitable bioisostere for the aryl (heteroaryl) ring present in aryl(heteroaryl)acetic acid non-steroidal antiinflammatory drugs.

Design and syntheses of methyl 2-methyl-2-[2-(4-benzoyl-5-phenyl-7-halo-2-azabicyclo[4.1.0]hept-3-ene)]acetates: novel inhibitors of cyclooxygenase-2 (COX-2) with analgesic-antiinflammatory activity

Design and syntheses of methyl 2-methyl-2-[2-(4-benzoyl-5-phenyl-7-halo-2-azabicyclo[4.1.0]hept-3-ene)]acetates: novel inhibitors of cyclooxygenase-2 (COX-2) with analgesic-antiinflammatory activity

Synthesis and analgesic-antiinflammatory activity of certain fluorinated cinchophen analogs

Cinchopen, 2-phenyl-4-quinolinecarboxylic acid (I) is one of the early introduced drugs for treatment of gout (1). It possesses analgesic, antipyretic, anti-inflammatory and uricosuric activity (2). However, the drug is currently not used clinically since it was found to produce hepatic damage (3,4). This paper describe the synthesis certain fluorinated cinchophen analogs (II) that may have patent desired pharmacological activity but devoid of the undesired side effects. Detailed synthesis and pharmacological evaluation of those compound will be presented. Also the effect of fluorine introduction as to the analgesic activity of this class of compounds will be also discussed. ▪

ChemInform Abstract: Carboxymethyl and Carboxy Derivatives of 7H- and 5H-1,2,4-Triazolo-(3,4-b)(1,3,4)thiadiazine: Synthesis and Biological Evaluation.

Some carboxymethyl- and carboxy-derivatives of 7H- and 5H-1,2,4-triazolo [3,4-b][1,3,4] thiadiazine were prepared. Their structure are discussed on the basis of IR, NMR and mass spectra. The synthesized compounds were subjected to a preliminary pharmacological screening for antiinflammatory-analgesic activity and to microbiological test on various species of mycetes and bacteria.

Antibiotic and Anti-inflammatory Analgesic Activities of Harungana madagascariensis Stem Bark

AbstractThis study shows that the aqueous methanol extract of Harungana madagascariensis has a broad spectrum antibiotic activity, decreases greatly the reaction time of mice to heat, inhibits carrageenan induced rat-paw oedema, and inhibits prostaglandin synthetase activity in vitro.

Synthesis and analgesic-antiinflammatory activity of some 4- and 5-substituted heteroarylsalicylic acids

We have made a series of 4- and 5-aryl- and 4- and 5-heteroarylsalicylic acid derivatives with the objective of reducing gastric irritation and increasing potency. Here we describe a series of 4- and 5-heterocyclic salicylic acids and their antiinflammatory-analgesic potencies measured in comparison to aspirin. An improvement of the therapeutic index over aspirin of 100 was achieved; however, the heterocyclic salicylic acids lacked antipyretic activity. Some physicochemical parameters which may bear on the antiinflammatory activity of these compounds are discussed.