benzofurans and Edema

Topics: Bacillus; Benzofurans; Benzophenanthridines; Biomarkers; Dibenzofurans, Polychlorinated; Edema; Eosinophilia-Myalgia Syndrome; Food Contamination; Food Handling; Foodborne Diseases; History, 20th Century; Humans; Isoquinolines; Mustard Plant; Oryza; Plant Oils; Polychlorinated Biphenyls; Risk Factors

Topics: Abnormalities, Drug-Induced; Animal Diseases; Animals; Benzofurans; Biphenyl Compounds; Cattle; Cattle Diseases; Chemical and Drug Induced Liver Injury; Chickens; Dermatitis, Occupational; Dioxins; Edema; Environmental Exposure; Herbicides; Humans; Hydrocarbons, Halogenated; Poultry Diseases

Topics: Benzbromarone; Benzofurans; Chronic Disease; Clinical Trials as Topic; Edema; Female; Fibrinolytic Agents; Humans; Leg; Male; Venous Insufficiency

Spinal cord injury (SCI) is a devastating disease inflicting lifetime disability to the victims. Military personnel are quite often victims of SCI for which no suitable therapeutic strategies have been developed so far. The main reason for SCI induced disability is loss of neural connections below and above the lesion site causing motor paralysis and somatosensory disturbances Loss of neuronal connections thwart spinal cord conduction resulting in motor function disability. To enhance spinal cord conduction grafting of peripheral nerves, implant of hydrogels filled with neuroprotective drugs is used but so far, no satisfactory results re achieved. In this regards implants of microelectrode for enhancing tissue connectivity is suggested that is still under experimental state. We have used titanium implant with or without TiO

Topics: Animals; Benzofurans; Capillary Permeability; Drug Delivery Systems; Drug Implants; Edema; Evoked Potentials; Locomotion; Male; Nanostructures; Nanowires; Neuroprotective Agents; Rats; Spinal Cord Injuries; Titanium

BACKGROUND Salvianolic acid B (SB) is a major active phyto-component of the plant Radix Salvia miltiorrhiza, which is traditionally used to treat joint pain and arthritis. The present study examined the anti-rheumatoid arthritis efficacy of SB on collagen-induced rheumatoid arthritis (CIA) in a rat model. MATERIAL AND METHODS Forty-eight rats were divided into 4 groups: Control rats treated with saline (Group I), rats subjected to CIA induction by intradermal injection of bovine collagen II type at the tail (Group II), and rats subjected to CIA and supplemented with either 20 or 40 mg/kg of SB for 28 days (group III or IV). RESULTS Paw swelling, edema, arthritis score, thymus and spleen indexes, and neutrophil infiltration were significantly decreased (p<0.01) by treatment with 20 or 40 mg/kg of SB. The levels of inflammatory cytokines (interleukin-1β, -6, and -17, and TNF-α) and anti-collagen II-specific immunoglobulins (IgG1 and IgG2a) were markedly decreased (p<0.01), and those of antioxidant enzymes (SOD, CAT, and GSH) were significantly increased (p<0.01) in SB-treated rats. Administration with SB (20 or 40 mg/kg) resulted in lower phosphorylated IkB-a and NF-κB p65 protein levels and markedly downregulated IκB-a expression. Furthermore, CIA rats revealed the presence of highly diffused polymorphonuclear cells (PMNs) infiltration with eroded cartilage; however, these phenomena were considerably ameliorated by SB. CONCLUSIONS SB alleviates oxidative stress and inflammation in CIA rats, thus verifying its anti-rheumatoid arthritis property.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Benzofurans; Disease Models, Animal; Down-Regulation; Edema; Inflammation; Inflammation Mediators; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Transcription Factor RelA

A protocol was established to produce bioactive compounds in a callus culture of

Topics: Ageratina; Animals; Anti-Inflammatory Agents; Benzofurans; Culture Techniques; Ear; Edema; Ethanol; Interleukin-6; Kinetin; Lipopolysaccharides; Male; Mice; Naphthaleneacetic Acids; NF-kappa B; Nitric Oxide; Pentacyclic Triterpenes; Phospholipases A2; Plant Extracts; Plant Leaves; RAW 264.7 Cells; Secondary Metabolism; Solvents; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

New molecular hybrids combining benzothiophene or its bioisostere benzofuran with rhodanine were synthesized as potential dual COX-2/5-LOX inhibitors. The benzothiophene or benzofuran scaffold was linked at position -2 with rhodanine which was further linked to various anti-inflammatory pharmacophores so as to investigate the effect of such molecular variation on the anti-inflammatory activity. The target compounds were evaluated for their in vitro COX/LOX inhibitory activity. The results revealed that, compound 5h exhibited significant COX-2 inhibition higher than celecoxib. Furthermore, compounds 5a, 5f and 5i showed COX-2 inhibitory activity comparable to celecoxib. Compound 5h showed selectivity index SI=5.1 which was near to that of celecoxib (SI=6.7). Compound 5h displayed LOX inhibitory activity twice than that of meclofenamate sodium. Moreover, compounds 5a, 5e and 5f showed significant LOX inhibitory activity higher than that of meclofenamate sodium. Compound 5h was screened for its in vivo anti-inflammatory activity using formalin-induced paw edema and gastric ulcerogenic activity tests. The results revealed that, it showed in vivo decrease in formalin-induced paw edema volume higher than celecoxib. It also displayed gastrointestinal safety profile as celecoxib. The biological results were also consistent with the docking studies at the active sites of the target enzymes COX-2 and 5-LOX. Also, compound 5h showed physicochemical, ADMET, and drug-like properties within those considered adequate for a drug candidate.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Benzofurans; Catalytic Domain; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Edema; Formaldehyde; Lipoxygenase Inhibitors; Male; Molecular Docking Simulation; Molecular Structure; Rats; Rats, Wistar; Rhodanine; Structure-Activity Relationship; Thiophenes

Chalcone (3) has been synthesized as a new chalcone derivative bearing benzofuran moiety at 1 position. Such chalcone was used as a model dielectrophile applied to react with some nucleophiles such as 5-amino pyrazoles, 5-amino-1,2,4-triazole, 2-aminobenzimidazole, and 6-uraciles under Michael reaction conditions and resulted in a new series of fused pyrimidines such as pyrazolo[1,5-a]pyrimidines 7a-e, [1,2,4]-triazolo[1,5-a]pyrimidine 9, pyrimido[1,2-a]benzimidazole 11, and synthesis of pyrido[2,3-d]pyrimidinones 13a and b. The structures of the synthesized target heterocyclic compounds were confirmed by microanalytical and spectral data such as Fourier transform (FT)-IR, (1)H-NMR, and MS spectra. The newly synthesized compounds were evaluated for their anti-inflammatory and antimicrobial activities; most showed significant activities.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Aspergillus niger; Benzofurans; Candida albicans; Carrageenan; Dose-Response Relationship, Drug; Edema; Escherichia coli; Fusarium; Mice; Microbial Sensitivity Tests; Molecular Structure; Pseudomonas aeruginosa; Pyrimidines; Staphylococcus aureus; Structure-Activity Relationship

Investigation of the pharmacological potential of Tetrahydrofurano/pyrano quinoline and Benzo [b]furoindolyl derivatives in acute inflammation, pain and oxidative stress.. Tetrahydrofurano/ pyrano quinoline and Benzo[b]furoindolyl were evaluated for anti-inflammatory activity by carrageenan-induced hind paw edema in rats. Analgesic activity in mice was assessed by both peripheral and central analgesic models. The free radical scavenging activity of the synthetic compound was analyzed by the in vivo antioxidant assays, by measuring the antioxidant enzymes such as Superoxide dismutase (SOD), Catalase and Peroxidase from the liver homogenate and the in vitro antioxidant activity was evaluated by DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assay.. The compounds had substantially inhibited the inflammation induced by subcutaneous carrageenan injection. The same compounds had demonstrated remarkable central and peripheral analgesic activity with potent free radical scavenging activity as evident from both in vitro and in vivo antioxidant assays.. Tetrahydrofurano/pyrano quinoline and Benzo[b]furoindolyl derivatives exhibit varied pharmacological activities that include anti-inflammatory, analgesic and antioxidant activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Benzofurans; Carbon Tetrachloride; Carrageenan; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Drug Design; Edema; Furans; Indoles; Lipid Peroxidation; Liver; Mice; Oxidative Stress; Pain; Quinolines; Rats

This study evaluated the potential anti-inflammatory effects of natural phthalides, isolated from Ligusticum porteri, and of semi-synthetic phthalides. Anti-inflammatory activity was investigated in two mouse models; one with ear edema, induced with 12-O-tetradecanoylphorbol-13-acetate, and the other with paw edema, induced with carrageenan. The effect on the RAW 264.7 stimulated with lipopolysaccharide cells was evaluated and after application of 12-O-tetradecanoylphorbol-13-acetate, the activity of myeloperoxidase was assessed to serve as an index of leukocytes infiltration together with the histological evaluations. We also assessed the inhibition of cyclooxygenases 1 and 2 in vitro. Our results demonstrated that administration of semi-synthetic phthalides significantly inhibited the ear edema induced by 12-O-tetradecanoylphorbol-13-acetate, and reduced the paw edema caused by carrageenan. The anti-inflammatory activity of phthalides could, in part, be explained by the reduction in myeloperoxidase activity and the infiltration of leukocytes. The semi-synthetic phthalides also inhibited the production of oxide nitric in RAW cells.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Biological Products; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Edema; Inflammation; Male; Mice; Nitric Oxide Synthase; Nitrites; Peroxidase; RAW 264.7 Cells; Skin; Tetradecanoylphorbol Acetate

Benzofuranone (BF1) was synthesized and its effects evaluated on mechanical hypersensitivity and paw edema models induced by different agents and on neuropathic pain induced by partial ligation of the sciatic nerve. An attempt was also made to elucidate the mechanism of action.. Swiss mice were used for the tests. Hypersensitivity was induced by intraplantar injection of carrageenan, bradykinin (BK), prostaglandin E2 (PGE2), epinephrine, lipopolysaccharide, or complete Freund adjuvant or by using a neuropathic pain model (evaluated with von Frey filament 0.6 g). The antiinflammatory effects were investigated in a paw edema model induced by carrageenan, PGE2, and BK (measured with a plethysmometer). The involvement of protein kinase C (PKC) was investigated through a nociception model induced by phorbol myristate acetate.. BF1 inhibited the hypersensitivity and paw edema induced by intraplantar injection of carrageenan, BK, and PGE2 (P < 0.001), and it was effective in reducing the hypersensitivity evoked by complete Freund adjuvant or epinephrine (P < 0.001) but not by lipopolysaccharide (P = 0.2570). BF1 inhibited the licking behavior induced by phorbol myristate acetate (P < 0.001), suggesting involvement of the PKC pathway. A reduction in hypersensitivity of mice submitted to partial ligation of the sciatic nerve (P < 0.001) was observed, with inhibition of neutrophil migration and interleukin-1β production into the spinal cord. BF1 treatment did not interfere with locomotor activity (P = 0.0783) and thermal withdrawal threshold (P = 0.5953), which are important adverse effects of other analgesics.. BF1 has dose-dependent antihypersensitive and antiinflammatory effects in both acute and chronic models of pain and inflammation, possibly mediated through interference with the PKC activation pathway. The easy and fast synthesis of this compound, low-cost, low-concentration-requirement, and once-daily-administration drug suggest it as a candidate for future clinical studies.

Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Benzofurans; Disease Models, Animal; Edema; Female; Male; Mice; Pain; Protein Kinase C; Signal Transduction

New series of furosalicylic acids 3a-c, furosalicylanilides 6a-n, furobenzoxazines 8a-f, 1-benzofuran-3-arylprop-2-en-1-ones 12a,b, 6-(aryl-3-oxoprop-1-enyl)-4H-chromen-4-ones 16a-c and 6-[6-aryl-2-thioxo-2,5-dihydropyrimidin-4-yl]-4H-chromen-4-ones 17a-c were synthesized. Anti-inflammatory activity evaluation was performed using carrageenan-induced paw edema model in rats and prostaglandin E(2) (PGE(2)) synthesis inhibition activity. Some of the tested compounds revealed comparable activity with less ulcerogenic effect than Diclofenac at a dose 100 mg/kg. All the synthesized compounds were docked on the active site of cyclooxygenase-2 (COX-2) enzyme and most of them showed good interactions with the amino acids of the active site comparable to the interactions exhibited by Diclofenac.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Benzopyrans; Binding Sites; Carrageenan; Catalytic Domain; Computer Simulation; Cyclooxygenase 2; Diclofenac; Dinoprostone; Disease Models, Animal; Edema; Gene Expression Regulation; Male; Rats; Rats, Wistar

Myagropsis myagroides has been used as a Chinese medicine and its extract has shown various biological activities, however, its anti-inflammatory mechanism remains unknown. In this study, we investigated the inhibitory effects of the ethyl acetate fraction of M. myagroides (EFM) on the production of inflammatory mediators and pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. EFM significantly inhibited LPS-induced production of nitric oxide (NO), prostaglandin E(2), and pro-inflammatory cytokines in a dose-dependent manner and suppressed the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in RAW 264.7 cells. Inhibitory effect of EFM on iNOS expression and NO production was further confirmed using LPS-activated mouse peritoneal macrophages. EFM treatment strongly suppressed the activation of nuclear factor-kappa B (NF-κB) by suppressing phosphorylation of Akt and extracellular signal-regulated kinases (ERKs). EFM as well as phlorofucofuroeckol B (PFF-B), a major compound isolated from EFM, reduced ear edema induced by phorbol 12-myristate 13-acetate in mice. These results indicate that the anti-inflammatory effect of EFM, rich in PFF-B, on LPS-stimulated macrophages is regulated by the inhibition of NF-κB pathway through the inhibition of ERKs and Akt phosphorylation in LPS-stimulated macrophage cells.

Topics: Animals; Benzofurans; Cell Line; Cell Survival; Dioxins; Edema; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred ICR; Molecular Structure; Phaeophyceae

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID₅₀ 77 μg/cm²) as well compounds 1-11 (ID₅₀ 0.31-0.60 μmol/cm²) exhibited topical antiedematous properties comparable to those of indomethacin (ID₅₀ 0.29 μmol/cm²) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E₂ synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Austria; Benzofurans; Cyclooxygenase 1; Edema; Intramolecular Oxidoreductases; Krameriaceae; Lignans; Male; Mice; NF-kappa B; Plant Roots; Prostaglandin-E Synthases

It is reported that dihydroxy chalcones have analgesic and anti-inflammatory effects. Study of the structure activity relationship (SAR) shows that benzofuran-3-one derivatives may be more effective in this respect. In this study, a new (Z)-2-(3,4-dihydroxybenzylidene)-5-methoxybenzofuran-3(2H)-one (compound 5) was synthesized and its analgesic and anti-inflammatory effects were evaluated by formalin, carrageenan and hot-Plate methods in mice. The results showed that, compound 5 induced significant antinociceptive and anti-inflammatory effect (P<0.01). Maximum analgesia (42.6%) was obtained at dose of 25 mg/kg in the first phase of formalin test. The effect of compound 5 was higher (87.7%) in chronic phase of inflammation induced by formalin (P<0.01). Administration of 25 mg/kg of compound 5 inhibited the inflammation induced by carrageenan, 32.8% and 41.7%, 1 and 3 hour after carrageenan injection, respectively. In addition, this dose of compound 5, induces significant analgesia (20.2%) in hot plate test 45 minutes after injection (P<0.01). Therefore it seems that compound 5 has potential for discovery of a compound with potent anti-inflammatory and analgesic effects and its scaffold could be use for further structural modifications.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents; Benzofurans; Carrageenan; Chalcone; Dose-Response Relationship, Drug; Edema; Foot; Formaldehyde; Hot Temperature; Male; Mice; Pain Measurement

Treatment of 2-bromoacetylbenzofuran (2) with pyridine afforded its corresponding pyridinium bromide 3. The latter salt reacted with some activated alkenes and acetylenes to give the corresponding indolizine derivatives. Treatment of the salt 3 with benzylidenemalononitriles 9 afforded polysubstituted aniline derivatives, however with arylidenecyanothioacetamides 15 it gave the corresponding 4,5-dihydrothiophenes. Bromide 3 also coupled with p-chlorobenzenediazonium salt followed by ammonium acetate to give the corresponding 1,2,4,5-tetrazine derivative. The biological activity of the newly synthesized compounds was examined and some of them were found to possess anticonvulsant and anti-inflammatory activities.

Topics: Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Benzofurans; Edema; Mice; Rats; Structure-Activity Relationship

This study was performed to assess the efficacy of alpha-viniferin (Carex humilis Leyss) on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced by a single subcutaneous injection of 0.1 ml complete Freund's adjuvant (CFA) containing 7.5 mg Mycobacterium butyricum suspended in 1 ml sterile paraffin oil into the right hind paw. Forty female Sprague-Dawley rats were injected. Righting reflex was uniformly lost and considered to be the initial point of arthritis development on day 7 after CFA injection. Rats were divided into four groups, and upon development of arthritis, tested groups were orally administered 3 or 10 mg/kg alpha-viniferin or 10 mg/kg ketoprofen every day for 14 days. The control group was orally administered 2 ml of physiological saline solution. Bone mineral density (BMD), radiological changes and edematous volumes were measured for 35 days. Alpha-viniferin suppressed the development of inflammatory edema, and inhibited the bone destruction, noted with a decrease in BMD (p < 0.05). Hind paw edema volume, BMD and radiological changes did not differ significantly in the ketoprofen and alpha-viniferin groups during the entire study period. In conclusion, alpha-viniferin suppressed arthritic inflammation and bony change in rats.

Topics: Animals; Arthritis, Experimental; Benzofurans; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Edema; Female; Femur; Ketoprofen; Plant Extracts; Rats; Rats, Sprague-Dawley; Tibia

We have synthesized and characterized some oxidative metabolites of S-2474. In this study, we discovered a novel skeleton, the 2,3-dihydrobenzofuran derivative, which inhibited PGE(2) production at a very low concentration and was effective in the anti-carrageenin footpad edema assay.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cyclic S-Oxides; Dinoprostone; Edema; Humans; Interleukin-1; Leukotriene B4; Lipoxygenase Inhibitors; Microsomes, Liver; Rats; Thiazoles

The anti-inflammatory activity of alpha-viniferin, a trimer of resveratrol, has been demonstrated in an animal model of carrageenin-induced paw edema, and inhibitory effects of the compound on cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) have been investigated in order to understand the mode of the observed action. alpha-Viniferin at doses > 30 mg/kg ( p. o.) or > 3 mg/kg ( i. v.) showed significant anti-inflammatory activity on carrageenin-induced paw edema in mice. alpha-Viniferin showed an inhibitory effect with an IC (50) value of 4.9 microM on COX-2 activity but a very weak inhibitory effect with 55.2 +/- 2.1 % of the control (100 %) at 100 microM on COX-1 activity. alpha-Viniferin at doses of 3 microM to 10 microM inhibited the synthesis of COX-2 transcript in lipopolysaccharide (LPS)-activated murine macrophages Raw264.7. alpha-Viniferin showed an IC50 value of 2.7 microM on nitric oxide (NO) production in LPS-activated Raw264.7 cells when alpha-viniferin and LPS were treated simultaneously, but did not inhibit the NO production when alpha-viniferin was treated at 12 h after LPS stimulation. alpha-Viniferin inhibited synthesis of iNOS transcript with an IC50 value of 4.7 microM. Consequently, the inhibitory effect of alpha-viniferin on the release of prostanoids and NO could play an important role to show anti-inflammatory action.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Caragana; Carrageenan; Cell Line; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; DNA Primers; Dose-Response Relationship, Drug; Edema; Inhibitory Concentration 50; Injections, Intravenous; Isoenzymes; Macrophages; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phytotherapy; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; Stilbenes

20 compounds were isolated from the leaves of Magnolia denudata including 16 lignans, which belong to 6 structural types. Except for (7R, 8S, 1'S)-delta8' -1', 4'- dihydro-5'-methoxy-3,4-methylenedioxy-4'-oxo-7.0.2', 8.1'-neolignan (6), magliflonenone (9), 2, 5'-diene-2', 8'-epoxy-5'-methoxy-8-methyl-4'-oxo-3,4- methylenedioxy-spiro (5, 5)-undecane (10), veraguensin (16) and beta-sitosterol (20), the other 15 compounds were obtained from this species for the first time. The absolute configurations of 3 compounds (1, 4, 10) were determined by CD spectroscopy for the first time. The anti-inflammatory activities of compounds 1, 2 and 16 were assessed and 2 was shown to have significant inhibition effect on mice hind-paw edema induced by carrageenan.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; China; Edema; Gas Chromatography-Mass Spectrometry; Lignans; Magnoliaceae; Mice; Nuclear Magnetic Resonance, Biomolecular; Optical Rotation; Plant Extracts; Plant Leaves; Spectrophotometry, Infrared

(+)-Usnic acid, isolated from the lichen Roccella montagnei, showed a dose-dependent anti-inflammatory activity when tested on rats, employing acute and chronic models.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Carrageenan; Dose-Response Relationship, Drug; Edema; Female; Fungi; Gossypium; Granuloma, Foreign-Body; Humans; Ibuprofen; Male; Plants, Medicinal; Rats; Rats, Wistar

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were prepared and evaluated as potential nonsteroidal antiinflammatory and analgesic agents. Interest in this class of compounds arose when a DHDMBF was found to be an active metabolite of the di-tert-butylphenol antiinflammatory agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs have good in vivo antiinflammatory and analgesic activity after oral administration. These compounds inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) in vitro. The cyclooxygenase inhibition was found to be selective for the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX inhibition may be responsible for the gastrointestinal safety of compounds such as 30.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Blood Platelets; Carrageenan; Cyclooxygenase Inhibitors; Edema; Humans; Lipoxygenase Inhibitors; Male; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were found to be nonsteroidal antiinflammatory and analgesic agents. These compounds are inhibitors of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX) with selectivity for the COX-2 isoform. A series of analogues were prepared to investigate the scope of this lead. Five ketone side chains from active DHDMBFs were used to investigate the effects of changes in the DHDMBF "core": the size and identity of the heterocycle and the substituent requirements of the heterocycle and phenyl ring. Biological testing showed that a variety of structural changes can be accommodated, but no structure was clearly superior to the DHDMBF structure.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Benzofurans; Blood Platelets; Carrageenan; Cyclooxygenase Inhibitors; Edema; Humans; Lipoxygenase Inhibitors; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley

We report an expansion of the scope of our initial discovery that 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) are antiinflammatory and analgesic agents. Several other functional groups have been introduced at the 5 position: amides, amidines, ureas, guanidines, amines, heterocycles, heteroaromatics, and heteroaryl ethenyl substituents in the 5 position all provide active compounds. These compounds are dual cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitors. They inhibit both COX-1 and COX-2 with up to 33-fold selectivity for COX-2.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Edema; Enzyme Inhibitors; Humans; Isoenzymes; Lipoxygenase Inhibitors; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Rats; Structure-Activity Relationship

A structure-activity study was carried out for some new antiinflammatory compounds 2,3-dihydrobenzo-furan-2-ones, analogues of the natural product wortmannin (the mold metabolite), inhibitors of prostaglandin synthesis. The results show that lipophilicity and steric properties are very important in two testing models.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Benzofurans; Carrageenan; Disease Models, Animal; Drug Design; Edema; Models, Chemical; Prostaglandins; Rats; Structure-Activity Relationship

2-Methyl-5-(3-phenylpropionyl)-1-benzoxolane (CAS 159264-96-7) was synthesized and studied for anti-inflammatory properties. This new aryl ketone was more active than the previously reported 5-acyl substituted 1-benzoxolanes except 5-cinnamoyl-2-methyl-1-benzoxolane (the unsaturated analogue) which exhibited similar anti-inflammatory activity and similar toxicity but was more gastrotoxic. Anti-inflammatory and analgesic effects of 2-methyl-5-(3-phenylpropionyl)-1-benzoxolane were less pronounced than those of indometacin but greater than those of acetylsalicylic acid (ASA). The new ketone was less toxic and less gastrotoxic than both the reference drugs mentioned above. Therapeutic indices of the new compound were significantly greater than those of ASA and indometacin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bentonite; Benzofurans; Carrageenan; Edema; Gossypium; Granuloma; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred BALB C; Pain Measurement; Rats; Rats, Wistar; Spectrophotometry, Ultraviolet; Stomach Ulcer

Two previously undescribed elemanolide esters, the 2-methylpropanoate and 2-methyl-2-propenoate of 11,13-dehydromelitensin, were isolated in the course of a bioassay-guided fractionation from the aerial parts of Centaurea chilensis Hook. et Arn., used traditionally to treat 'gout and rheumatism'. The mixture of both substances exhibits anti-inflammatory activity in the carrageenan-induced paw edema assay.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Carrageenan; Chile; Edema; Female; Guinea Pigs; Male; Plant Extracts; Plants, Medicinal

A series of new 7-acyl substituted 1-benzoxepanes and 5-acyl substituted 2-methyl-1-benzoxolanes were synthesized and studied for anti-inflammatory properties. The benzoyl derivatives were more active than the corresponding halogenobenzoyl derivatives and previously reported structural analogues containing less methylene groups in their heterocyclic ring. The introduction of a methyl group at the 2-position of 5-cinnamoyl-1-benzoxolane heterocyclic ring significantly potentiated the activity. Anti-inflammatory and analgesic effects of 7-benzoyl-1-benzoxepane and 5-cinnamoyl-2-methyl-I-benzoxolane were less pronounced than those of indomethacin and diclofenac but greater than those of acetylsalicylic acid (ASA). Both compounds were less toxic and 5-cinnamoyl-2-methyl-1-benzoxolane was also less gastrotoxic than all the reference drugs mentioned above. Therapeutic indices of 5-cinnamoyl-2-methyl-1-benzoxolane were greater than those of diclofenac and significantly greater than those of ASA and indomethacin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Bentonite; Benzofurans; Benzoxepins; Carrageenan; Chemical Phenomena; Chemistry, Physical; Edema; Gastric Mucosa; Granuloma; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Necrosis; Peritonitis; Rats; Rats, Wistar

IRFI 016 has demonstrated significant antioxidant activity, inhibiting hepatic lipid peroxidation (rat intoxicated by CCl4) and the formation of gastric lesions by ethanol (rat). This activity proved equal to or better than that exhibited by the most investigated antioxidant/radical scavenger agents (such as BHA, BHT, Vitamin E). The drug markedly increased mucus production (rabbit, mouse) by all the administration routes used (os, i.v. and inhalatory) and proved more active than, or overlapping, the most noted mucoregulatory/mucolytic drugs (sobrerol, bromexine, thiopronine, ambroxol, N-acetylcysteine) which were chosen for comparison. The tracheo-bronchial mucus viscosity was also significantly reduced (bronchitic animals) as was the fucose and total protein content. In the pigeon, IRFI 016 improved mucociliary clearance. Moreover IRFI 016 evidenced anti-inflammatory activity nearly equal to that exhibited by ASA and phenylbutazone (carrageenin oedema, abcesses and inflammatory pain).

Topics: Abscess; Animals; Antioxidants; Benzofurans; Bronchi; Carbon Tetrachloride Poisoning; Carrageenan; Columbidae; Edema; Ethanol; Expectorants; Female; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred Strains; Mucus; Pain; Rabbits; Rats; Rats, Inbred Strains; Stomach; Trachea; Vitamin E

The roots of Caragana chamlagu Lamarck (Leguminosae) are used as an anti-neuralgic, anti-rheumatic, anti-arthritic, etc. in the folk medicine of Korea. An ether extract was fractionated with monitoring of the anti-inflammatory activity, and the active principle was elucidated as (+)-alpha-viniferin on the basis of spectroscopic data, including two-dimensional nuclear magnetic resonance and circular dichroism spectra.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Carrageenan; Edema; Korea; Male; Mice; Plants, Medicinal

Platelet activating factor (PAF), a potent lipid-like vasoactive agent, induced rat foot edema when it was injected subplantarly. The edema reached its maximum 1 h after PAF challenge. Indomethacin did not inhibit the peak edematous response whereas both PAF antagonists, kadsurenone and L-652,731, inhibit the PAF-induced rat foot edema (PFE). Both PAF antagonists also partially block the first phase of the carrageenin-induced rat foot edema (CFE). Using the inhibition of [3H]PAF receptor binding to prepared rabbit platelet membranes, release of PAF or PAF-like materials in carrageenin-injected rat hindpaw was observed. These results suggest that the released PAF or PAF-like materials together with the released histamine and kinin evoke the first phase hindpaw edema in the rats. Indomethacin or PAF antagonist, administered alone, does not block the first phase or the second phase of CFE, respectively. However, PAF antagonist potentiated the inhibitory effects of indomethacin suggesting that the released PAF may also be involved in the biosynthesis of prostaglandins to initiate the second phase of rat CFE.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Benzopyrans; Carrageenan; Edema; Lignans; Male; Platelet Activating Factor; Rats; Rats, Inbred Strains; Time Factors

A series of 2,3-dihydrobenzofuran-2-one analogues of the mold metabolite wortmannin, which is a powerful antiinflammatory compound, was synthesized. Most of these compounds were tested for their ability to inhibit the carrageenin paw edema and the adjuvant-induced arthritis of the rat and for their ability to inhibit prostaglandin synthesis in vitro. Indomethacin and diclofenac were used as references. The results show that compounds bearing an alkyl or aryl group in position 6 and an additional substituent, preferably chlorine, in position 5 are very powerful antiinflammatory agents and inhibitors of prostaglandin synthesis. The most active among these compounds, 5-chloro-6-cyclohexyl-2,3-dihydrobenzofuran-2-one, was significantly more potent than diclofenac in all testing models, more powerful than indomethacin in inhibiting acute inflammation and prostaglandin synthesis, and somewhat less potent than the latter compound in the adjuvant arthritis model.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Benzofurans; Cattle; Chemical Phenomena; Chemistry; Depression, Chemical; Edema; In Vitro Techniques; Male; Prostaglandins; Rats; Stomach Ulcer; Structure-Activity Relationship

1. Chloroform edema. On the backskin of a mouse a wheal was produced by locally applied chloroform containing a fluid rich in protein. It was investigated whether a series of edema-protective drugs, i.e., drugs with anti-inflammatory effect, corticoids, and vascular-active drugs, could inhibit the development of the wheal edema. Only benzarone proved a statistically significant inhibition. The fact that other drugs proved less effective or not at all, could be based on the difference between the mechansim of the chloroform edema and that of other edema models. A reciprocal effect between benzarone and chloroform may be considered as well. 2. Petechiae test. A vitamin C-free nutrition over 3 weeks did not increase the "brittleness of capillaries" in the backskin of guinea pigs; whereas 50 mg benzarone/kg fed daily over a period of 3 weeks caused a significant decrease in the number of petechiae compared to that in the controls. This effect, most likely, was not due to an improved stability of the capillaries but was based on the reduced blood circulation of the skin.

Topics: Animals; Ascorbic Acid Deficiency; Benzofurans; Chloroform; Edema; Guinea Pigs; Purpura

In chloralose-anesthetized cats, a hind-limb was perfused at constant flow and the vascular endothelium was made permeable for protein by intravascular injection of polidocanol and thiopental. Besides parameters of circulation and the transcapillary fluid exchange the contents of plasma protein and water were measured in skin and muscle tissue of the edematous hind-limb as well as in the contralateral untreated hind-limb. Benzarone, 2.5 mg/kg i.v., inhibited the development of the protein edemas when injected before the application of the edema producing substances. In polidocanol and thiopental-induced edemas--except for the thiopental-induced skin edema that was less marked even in the controls--benzarone had a significant effect.

Topics: Animals; Benzofurans; Blood Proteins; Cats; Edema; Muscles; Polyethylene Glycols; Skin; Thiopental

Topics: Benzofurans; Body Water; Cardiovascular System; Edema; Humans; Hypertension, Pulmonary; Oximes; Pulmonary Edema; Sodium Chloride

2-Carboxyaryl-substituted dihydrobenz[e]indoles, tetrahydroindoles, and tetrahydrobenzofurans have been synthesized as structural analogues of fendosal, a new antiinflammatory agent, and tested in the carrageenan-induced rat paw edema assay. Two of these, 2-(3-carboxy-4-hydroxyphenyl)-3-phenyl-4,5-dihydrobenz[e]indole and 1-(n-butyl)-2-(3-carboxy-4-hydroxyphenyl)-4,5,6,7-tetrahydroindole, were found to have significant activity, albeit of a lower order than fendosal.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Edema; Indoles; Male; Rats; Structure-Activity Relationship

Topics: Analgesics; Animals; Behavior, Animal; Benzofurans; Body Temperature; Drug Interactions; Edema; Lethal Dose 50; Male; Mice; Rats

A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and alpha-(7-chloro-2,2-dimethyl-2,3-dihydrobenzofuran)-alpha-methyl-5-acetic acid (13a) showed the most potent activity in this series.

Topics: Acetates; Animals; Anti-Inflammatory Agents; Benzofurans; Carrageenan; Edema; Gastric Mucosa; Inflammation; Male; Rats; Structure-Activity Relationship

The antiinflammatory activity of R-803 (alpha-methyl-3-phenyl-7-benzofuranacetic acid), a new nonsteroidal drug, has been demonstrated. The oral administration of R-803 inhibits carrageenan-induced edema of the rat's paw, ultraviolet-induced erythema of guinea-pig skin, adjuvant-induced and 6-sulfonamidoindazole-induced arthritides of the rat at doses in the range of 1.0 to 6.0 mg/kg. It also inhibits the cotton pellet-induced granuloma in the rat at higher doses.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Benzofurans; Edema; Erythema; Female; Granuloma; Guinea Pigs; Male; Radiation Injuries, Experimental; Rats; Ultraviolet Rays

Topics: Anilides; Animals; Benzofurans; Carbanilides; Dermatitis, Contact; Dioxins; Edema; Food Contamination; Gastrointestinal Diseases; Hexachlorophene; Hydrocarbons, Chlorinated; Immunosuppression Therapy; Naphthalenes; Neurologic Manifestations; Pesticide Residues; Photolysis; Polychlorinated Biphenyls; Polycyclic Compounds; Rats; Skin

Topics: Antihypertensive Agents; Benzofurans; Edema; Humans; Hyperthyroidism; Male; Middle Aged; Thiazoles

Topics: Adrenalectomy; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Benzofurans; Butyrates; Carrageenan; Dose-Response Relationship, Drug; Edema; Fever; Freund's Adjuvant; Inflammation; Male; Mycobacterium; Phenylbutazone; Rats; Rats, Inbred Strains; Time Factors; Yeasts

Topics: 2,4,5-Trichlorophenoxyacetic Acid; Abnormalities, Drug-Induced; Animals; Benzofurans; Chickens; Chromatography, Gas; Congresses as Topic; Dioxins; Dose-Response Relationship, Drug; Edema; Electron Spin Resonance Spectroscopy; Environmental Exposure; Environmental Health; Humans; Liver; Poultry Diseases; Spectrum Analysis; Structure-Activity Relationship; United States

Topics: Animal Feed; Animals; Benzofurans; Chickens; Chlorobenzenes; Chromatography, Gas; Dioxins; Disease Outbreaks; Edema; Fatty Acids; Food Additives; Food Contamination; Haplorhini; Pentachlorophenol; Phenols; Phenyl Ethers; Poultry Diseases; Spectrum Analysis; United States; United States Food and Drug Administration

Topics: Antihypertensive Agents; Benzofurans; Biopsy; Edema; Elastic Tissue; Histiocytes; Histocytochemistry; Humans; Pigmentation Disorders; Pigments, Biological; Skin

Topics: Acetylcholine; Animals; Anti-Inflammatory Agents; Benzofurans; Blood Coagulation; Bradykinin; Capillary Permeability; Capillary Resistance; Chronic Disease; Depression, Chemical; Dogs; Edema; Epinephrine; Female; Fibrinolysis; Fibrinolytic Agents; Guinea Pigs; Histamine H1 Antagonists; Mycobacterium Infections; Norepinephrine; Rabbits; Rats; Serotonin Antagonists; Stimulation, Chemical; Vascular Diseases

Topics: Aged; Benzofurans; Capillary Resistance; Edema; Humans; Male; Middle Aged; Mouth Neoplasms; Radiotherapy, High-Energy; Urinary Bladder Neoplasms