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A novel series of 1-(4-phenoxyphenyl)-3-[5-(substituted aryl)-1,3,4-oxa- diazol-2-yl]propan-1-one was synthesized by reaction of 3-(4-phenoxybenzoyl)propionic acid with several aryl acid hydrazides in phosphorus oxychloride. The structures of the compounds were supported by IR, 1H- and 13C-NMR, MS data and elemental analysis results. These compounds were tested for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. A few compounds were found to have very good anti-inflammatory activity in the carrageenan-induced rat paw edema test, while a fair number of the compounds showed significant analgesic activity in the acetic acid-induced writhing test. These new compounds showed very low ulcerogenic action with reduced malondialdehyde content (MDA), which is one of the by-products of lipid peroxidation.

Butenolide-based eighteen new amide derivatives ( 1-18) have been synthesized and evaluated for anti-inflammatory activity. The compounds 9, 17 and 4 exhibited significant in vivo inhibition of 84.69, 76.52 and 76.22 % inflammation, respectively, after 5 h without causing any damage to stomach and liver in comparison with the standard drug indomethacin which showed 79.04 % inhibition. The compounds showing potent anti-inflammatory activity were further evaluated for ex vivo TNF-α suppression. Compounds 9, 17 and 4 significantly suppressed TNF-α concentration to 74.83, 71.74 and 67.11 % as compared to indomethacin which exhibited a suppression of 69.01 %. Compounds 9 and 17 were also found to suppress the expression of COX-2 and NF-κB in the paw tissue. Moreover, compound 9 showed significant analgesic activity (57.03 %) which was comparable to indomethacin (61.03 %). [ABSTRACT FROM AUTHOR]

A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF- α target. Among all the docked molecules, compound 3f showed best glide score of −6.89. All the synthesized compounds were evaluated for in vivo anti-inflammatory activity by carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory activity were further tested for their in vitro TNF α expression. Compounds 3b and 2b were found to show significant inhibition of 76.22% and 71.47%, respectively after 5 h in comparison with standard drug indomethacin, which showed 80.98% inhibition of inflammation. Compounds 3b and 2b also suppressed TNF α level by 65.03% and 60.90% as compared indomethacin, which showed 68.84% of inhibition. Compound 3b showed significant analgesic activity of 60.04%, and its activity was comparable with indomethacin (64.04%). Compounds 3b and 2b were also tested for their effect on protein expression of COX-2 and NF- κB in the liver tissues. Compounds 3b and 2b were further evaluated for their gastric risk and lipid peroxidation action and showed superior GI safety along with reduction of LPO as compared to indomethacin. Hepatotoxicity study showed that these two compounds did not cause any damage to liver. [ABSTRACT FROM AUTHOR]

[Display omitted] The study aimed to synthesize and evaluate the potential anti-inflammatory and analgesic activities of rationally designed hybrid molecules of imidazolone and indole nuclei linked through a methylene bridge. Indolyl-imidazolone hybrids were synthesized in three simple steps starting from 2-phenyl-1 H -indole (1). In the first step, compound 1 was converted to 2-phenyl-1 H -indole-3-carbaldehyde (2) using standard conditions of the Vilsmeier Haack reaction. Benzoyl glycine was reacted with 2 (step 2) followed by treatment with aromatic/aliphatic amines (step 3) to furnish the indolyl-imidazolone hybrids. In vivo anti-inflammatory and analgesic activity along with ulcerogenicity of the prepared hybrids were evaluated in experimental animals. Molecular properties and pharmacokinetic profile were also predicted using online computational software. Cyclooxygenase-2 (COX-2) enzyme (PDB: 3pgh) was used for molecular docking studies. Indomethacin and aspirin were used as reference compounds for the comparison purpose. The percentage inhibition in edema in rats and reduction in frequency of acetic acid induced writhes in mice indicated that two compounds namely 3-(3-Hydroxpropyl)-2-phenyl-5-[(2-phenyl-1 H -indol-3-yl)methylene]-4 H -imidazol-4-one (4g) and 3-(2,4-Dinitrophenyl)-2-phenyl-5-[(2-phenyl-1 H -indol-3-yl) methylene]- 4 H -imidazol-4-one (4b) could be useful in treating pain and inflammatory conditions. Both the hybrid molecules exhibited better biological spectrum than the standard drug indomethacin. Additionally, both the potent compounds were noted to be less ulcerogenic than indomethacin. Pharmacokinetic profile predicted using ADMETsar and SwissADME cheminformatic software indicated compound 4g to be orally bioavailable with high blood brain barrier permeability. However, molecular docking studies revealed that compound 4b binds to COX-2 enzyme more strongly than 4g as indicated by a lower binding energy and formation of hydrogen bond interactions with amino acid residues in the binding pocket. It could be concluded that hybrid compounds 4b and 4g are promising lead candidates and should be further studied to develop compounds for the treatment of inflammatory conditions. [ABSTRACT FROM AUTHOR]

An ideal anti-inflammatory drug should have the desired effect in minimum dose with minimum side effects. Antimicrobial actions associated with such agents will be an added advantage as they broaden the spectrum of the compounds. Promising anti-inflammatory and antimicrobial activity together with low ulcerogenic properties of some 2(3 H)-furanones, synthesized in our previous study, prompted us to investigate the effect of the isobutyl group on their pharmacological profile. Since compounds 3, 9, 13, and 14 have both anti-inflammatory and analgesic effects in addition to low ulcerogenic incidence, they were selected for investigation of their inhibitory effects on various cyclo-oxygenase enzymes. It was found that they were more selective toward COX-2 enzymes. An MIC of 6.25 μg/mL was recorded for compounds 3, 13, and 14 against S. aureus, E. coli, R. oryza, and P. citrum. The study supports the development of furanone derivatives as potential anti-inflammatory agents with antimicrobial activity. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of a series of 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones derived from 4-oxo-4-(biphenyl-4-yl)butanoic acid (fenbufen) is described. The structures of these compounds were supported by IR, 1H NMR, mass spectrometric data and elemental analysis. These compounds were tested for their antiinflammatory, analgesic, ulcerogenic and lipid peroxidation actions. A few compounds were found to have very good antiinflammatory activity in carrageenan induced rat paw edema test, while a fair number of compounds showed significant analgesic activity in acetic acid induced writhing test. The newly synthesized compounds showed very low ulcerogenic action with reduced malondialdehyde (MDA) content, which is one of the byproducts of lipid peroxidation. In vitro COX-1 and COX-2 isozyme inhibition studies were also performed on some of the selected compounds. Compound 4i and 4h were found to be more selective towards COX-2 as indicated by COX-2 selectivity index of 36.06 and 29.05 (COX-2 IC50 =1.5μM and 1.8μM) respectively. [Copyright &y& Elsevier]

Abstract: A series of 3-arylidene-5-(4-chloro-phenyl)-2(3H)-furanones (2–13) and their nitrogen analogues 1-benzylpyrrolones (14–18) were synthesized. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. Some of the newly synthesized compounds showed good anti-inflammatory and analgesic activities with low GI toxicity and reduced lipid peroxidation. The biological activity was found to improve upon replacement of oxygen of furanone ring with benzylamine moiety i.e. 1-benzylpyrrolones. Similarly, compounds containing halogen group(s), compounds 15 and 17, showed higher degree of anti-inflammatory activity and their activity was comparable to that of the standard. These compounds showed interesting profile of analgesic activity in acetic acid induced writhing test (peripheral effect) and in the hot-plate test (central effect). The compounds were also tested for their ulcerogenic and lipid peroxidation action and showed superior GI safety profile along with reduction in lipid peroxidation as compared to that of the standard. [Copyright &y& Elsevier]

Abstract: 2-Arylidene-4-(4-phenoxy-phenyl)but-3-en-4-olides (1–17) were prepared from 3-(4-phenoxy-benzoyl)propionic acid and aromatic aldehydes. Some of the selected butenolides were reacted with ammonia and benzylamine to give corresponding 3-arylidene-5-(4-phenoxy-phenyl)-2(3H)-pyrrolones (18–23) and 3-arylidene-5-(4-phenoxy-phenyl)-1-benzyl-2(3H)-pyrrolones (24–29) respectively, which were characterized on the basis of 1H-, 13C-NMR, Mass spectrometric data and elemental analysis results. These compounds were tested for anti-inflammatory and antimicrobial actions. The compounds, which showed significant anti-inflammatory activity, were screened for their analgesic and ulcerogenic activities. Five new compounds (5, 6, 7, 25 and 26), out of 29 showed very good anti-inflammatory activity in the carrageenan induced rat paw edema test, with significant analgesic activity in the acetic acid induced writhing test together with negligible ulcerogenic action. Antibacterial activity against Staphylococcus aureus and Escherichia coli as well as antifungal activity against Candida albicans were expressed as the corresponding minimum inhibitory concentration (MIC) values. Compound 21, 22 and 23 showed excellent activity against C. albicans with MIC-10 μg/ml. Out of the above-mentioned compounds, 22 and 23 also showed good activity against S. aureus with MIC-20 and 15 μg/ml respectively. [Copyright &y& Elsevier]

Abstract: A series of 6-aminomethyl-2-aryl-1-benzopyran-4-one derivatives (10–24) were synthesized. The compounds were tested for anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. Among the tested compounds, six compounds 11, 13, 16, 18, 21 and 23 showed higher degree of anti-inflammatory activity (>75% activity of standard drug ibuprofen). In addition to remarkable anti-inflammatory activity, analgesic activity was found to be comparable with that of the standard drug ibuprofen. Compounds 16 and 21 showed a significant GI protection (with respect to ulcerogenesis) and a marked decrease in lipid peroxidation values whereas compounds 11 and 16 were found to possess antimicrobial activity against Staphylococcus aureus, Escherichiacoli, Rhizopus oryza and Penicillum citrum with an MIC of 10μg/mL. [Copyright &y& Elsevier]

A library of fourteen 2-imino-4-thiazolidinone derivatives ( 1a-1n ) has been synthesized and evaluated for in vivo anti-inflammatory activity and effect on ex-vivo COX-2 and TNF–α expression. Compounds 1k (5-(2,4-dichloro-phenooxy)-acetic acid (3-benzyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) and 1m (5-(2,4-dichloro-phenooxy)-acetic acid (3-cyclohexyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) exhibited in vivo inhibition of 81.14% and 78.80% respectively after 5 h in comparison to indomethacin which showed 76.36% inhibition of inflammation without causing any damage to the stomach. Compound 1k showed a reduction of 68.32% in the level of COX-2 as compared to the indomethacin which exhibited 66.23% inhibition of COX-2. The selectivity index of compound 1k was found to be 29.00 in comparison to indomethacin showing selectivity index of 0.476. Compounds 1k and 1m were also found to significantly suppress TNF-α concentration to 70.10% and 68.43% in comparison to indomethacin which exhibited 66.45% suppression. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Traditionally, Aporosa lindleyana Baill. has been used against various ailments viz . jaundice, fever, headache, seminal loss and insanity. The present study aims to evaluate the anti-inflammatory and anti-oxidant activity of the ethanolic extract of Aporosa lindleyana Baill. bark and its fractions. Method The anti-inflammatory activity of ethanolic extract of Aporosa lindleyana Baill. bark and its various fractions at doses of 200 mg/kg and 300 mg/kg b.w. has been carried out by a carrageenan induced hind paw edema method. To establish the probable mechanism of action, TNF-α and NO levels have been estimated by an ELISA method and the effect of active fraction on COX-2 and NF-κB expressions has been evaluated. The effect on the levels of anti-oxidative enzymes (CAT, SOD & GPX) by the ethanolic extract and its fractions has also been investigated. Furthermore, peptic ulcer and hepatotoxic risk evaluation has also been carried out at three times higher dose than that used in inflammatory in vivo model. Results Among the extract and its various fractions tested for anti-inflammatory activity, the methanolic fraction at a dose of 300 mg/kg showed significant inhibition in paw edema by 73% as compared to Indomethacin which showed 77% inhibition after 5 h. The same dose of methanolic fraction also caused significant reduction in TNF-α (59.27%) and NO concentration (57.12%) while Indomethacin showed inhibition of 63.91% and 60.12%. The active methanolic fraction was also found to inhibit the expression of NF-κB and COX-2 induced by carrageenan. Histological studies showed that the ethanolic extract and its fractions did not cause any damage to the stomach as well as to liver. Moreover, the active fractions also decreased lipid peroxidation levels and increased the antioxidant enzyme activities (SOD, CAT, GPX). Conclusion The results of present study demonstrated that significant anti-inflammatory activity of methanolic fraction of Aporosa lindleyana may be attributed to the modulation of pro-inflammatory mediators. Same fraction was also found to be effective against oxidative stress as it was found to elevate the levels of anti-oxidative enzymes. It can therefore be concluded that the methanolic fraction could be explored as a disease modifying agent against inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]