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Furanone, a five-membered heteroaromatic ring containing oxygen atom, is of immense pharmaceutical importance. Presence of this nucleus in biologically active compounds of natural and synthetic origin has made it an indispensable motif for design and development of new therapeutic agents. In recent years synthesis of furanone derivatives and exploring their therapeutic actions has been the prime interest amongst researchers. Furanone containing compounds cover numerous therapeutic categories viz. Analgesic and anti-inflammatory, anticancer, anticonvulsant, antibacterial and antifungal, antioxidant, antiulcer and anti-TB, etc. There is a need to couple recent work done with previously available information on furanone, a well acknowledged scaffold, to help scientists to develop novel and new furanone based therapeutic agents at a faster pace. This updated review highlights the worth of numerous therapeutically active furanone based compounds developed by the medicinal chemists. SAR studies have also been derived which may be useful for rational designing of furanone derivatives with improved therapeutic index. Image 1 • 2(5H) furanone derivatives emerged as the most promising anti-inflammatory, anti-cancer and anti-microbial agents. • The review covers useful pharmacological activities of furanone derivatives along with SAR studies. • It provides an overview of research work carried out on furanones in past three decades. • Enlist the patents granted on furanones and drugs containing furanone nucleus. [ABSTRACT FROM AUTHOR]

Abstract The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N -[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90 mg of brigatinib for 7 days and then 180 mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need. [ABSTRACT FROM AUTHOR]

The microstructural and metallurgical changes due to high temperature and high pressure applications, irradiations etc. cause a significant degradation of the mechanical properties of materials in refinery industries, nuclear industries, power plants, oil and gas pipe lines, aging aircrafts etc. That's why materials of in-service components in these industries need periodic health assessment to evaluate the degradation of mechanical properties. In the present work Finite Element simulation of indentation technique has been done for refinery materials by using ABAQUS FEM Code and different mechanical properties has been obtained. For properties evaluation by indentation test technique, some material constants is to be required. After carefully studying it has been found that in case of service exposed components there is a large difference between actual value of these material constants and assumed approximate values, this may be due to the fact that material constants change due to change in microstructure with the exposure to high temperature for a long time. This incorporates inaccuracy in property evaluation by indentation technique. The present work shows that properties obtained by using small punch test are quite accurate and that's why these properties can be used to find out Indentation Technique constants. This methodology is also developed here for finding out Indentation technique constants by using the value of yield strength & equation of true stress-true plastic strain curve obtained by using small punch test. In this way accuracy of Indentation technique can be increased. Thus a new methodology has been developed to find out the mechanical properties of service exposed components by clubbing the two techniques i.e. indentation technique, small punch technique. [ABSTRACT FROM AUTHOR]

A small library of twenty-four quinoline based butenolides also known as furanones and their nitrogen analogues was prepared by using two different aroylpropionic acids, viz. 3-(2-naphthoyl)propionic acid ( 3 ) and 3-(biphenyl-4-yl)propionic acid ( 4 ), as starting materials. The 3-aroylpropionic acids were reacted with different 6-substituted-2-chloroquinolin-3-carbaldehydes ( 2a–d ) to obtain the corresponding furan-2(3 H )-ones ( 5a–h ). The purified and characterized furanones were then converted into their corresponding 2(3 H )-pyrrolones ( 6a–h ) and N -benzyl-pyrrol-2(3 H )-ones ( 7a–h ). The antimicrobial activities of the title compounds were evaluated against two strains of each Gram +ve ( Staphylococcus aureus and Bacillus subtilis ), Gram −ve bacteria ( Escherichia coli and Pseudomonas aeruginosa ) and against fungal strains of Aspergillus niger and Aspergillus flavus . In vivo anti-inflammatory potential of the title compounds was investigated by standard method. Majority of the compounds showed significant antibacterial activity against both the Gram +ve strains. Eight most potent anti-inflammatory compounds ( 5b, 5d, 5h, 6b, 7b, 7d, 7f, 7h) which exhibited >53% inhibition in edema, were also screened for their in vivo analgesic activity. All the tested compounds were found to have significant reduction in ulcerogenic action but only three compounds ( 5d, 5h and 7h ) showed comparable analgesic activity to standard drug, diclofenac. The results were also validated using in silico approach and maximum mol doc score was obtained for compounds 7a–h . On comparing the in vivo and in silico anti-inflammatory results of synthesized compounds, N -benzyl pyrrolones ( 7a–h ) emerged as the potent anti-inflammatory agents. It was also observed that compounds that possess electron withdrawing group such as Cl or NO 2 are more biologically active. [ABSTRACT FROM AUTHOR]

[Display omitted] • Critical review on mix design, strength parameters, microstructures, and ANN application for GPC. • Key parameters influencing strength of GPC are assessed. • Artificial Neural Network – method used to predict the strength of GPC. • ANN showed as a promising tool in predicting the GPC compressive strength. Concrete is a combination of cement, sand, aggregate, and water. Cement manufacturing causes the generation of various gases, mainly greenhouse gases like CO 2 in the atmosphere. This CO 2 is the leading cause of global warming, so it becomes essential to find a replacement for cement in the construction industry and use more eco-friendly construction materials. Geopolymer concrete (GPC) has been growing in the last few decades due to several advantages, including improved strength, durability properties, and eco-friendly nature. The GPC consists of silica and alumina in large amounts with an alkaline solution. Due to the use of the alkaline solution to activate geopolymerisation reaction, it is called alkaline activated concrete (AAC). Herein, we reviewed the GPC material, mix proportion, strength influence parameters, and strength prediction method. In addition, an Artificial Neural Network (ANN) is proposed to predict the compressive strength of GPC incorporating various materials. The predicted results using varying machine learning tools such as ANN, GEP, DNN, ResNet, GEP etc., demonstrate the accuracy and performance evaluation of the model. Therefore, there is an urgent need to develop and employ machine learning tools to predict the strength parameters of GPC for various construction works. In summary, this literature review provides a direction to engineers involved in a wide range in the construction industry using GPC. [ABSTRACT FROM AUTHOR]

Objectives The study aimed to synthesize a mutual prodrug of norfloxacin and fenbufen with an objective of obtaining an effective and safer anti-inflammatory drug with useful antimicrobial actions. Methods An amide-based mutual prodrug ( NF-FN ) was prepared following a single-step synthesis by condensing norfloxacin with fenbufen under appropriate laboratory conditions. Its structure was established on the basis of IR, NMR, Mass spectral data and elemental analysis. The prodrug ( NF-FN ) was evaluated for in-vitro antibacterial activity against two gram positive ( Staphylococcus aureus & Bacillus subtilis ) and two gram negative bacterial strains ( Escherichia coli & Klebsiella pneumonia ). The in-vivo anti-inflammatory activity and ulcerogenicity of the synthesized prodrug were investigated in Wistar albino rats at the doses of 10 and 30 mg/kg body weight, respectively. Results The synthesized prodrug ( NF-FN ) showed very good activity against S. aureus & E. coli with MIC -6.25 μg/mL, and good activity against B. subtilis & K. pneumonia with MIC -12.5 μg/mL. Its anti-inflammatory activity was found to be better than that of the parent drug fenbufen. It was also observed to less severe on gastric mucosa in comparison to reference drug, fenbufen. Conclusion The prodrug showed promising results as anti-inflammatory agent however, its antibacterial action was found to be slightly weaker than the other parent drug norfloxacin. [ABSTRACT FROM AUTHOR]

The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives ( 3a–k ) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives ( 3a–k ) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine ( 3g ), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine ( 3i ) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine ( 3j ) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number ( 3i) emerged as a potential candidate for further research as it obeyed Lipinski’s rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. [ABSTRACT FROM AUTHOR]

Design and synthesis of new pyrimidine derivatives clubbed with thiazolidin-4-one from 4-(2-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidin-2-amine and their in vitro anticancer activities were screened at National Cancer Institute (NCI), USA against full NCI 60 cell lines. Compound 2 (NSC: 765735) exhibited remarkable growth inhibition at single dose (10 µM) and encourage chosen for broadcast at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 µM). The compound 2 was found better quality for Lung cancer cell line (HOP-92) by viewing growth inhibition (GI50 0.52) and no cytotoxicity seen (LC50 > 100). Molecular docking study was performed using Maestro 9.0 (Schrodinger Inc. USA) to provide binding mode into binding sites of CDK2. Compound 2 could be used as a lead compound for developing new potential anticancer agents. [ABSTRACT FROM AUTHOR]

Abstract: Liquid chromatography tandem mass chromatography (LC–MS/MS) is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC–MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches (column packing materials, column length and mobile phase) as well as different acquisition modes (SIM, MRM) for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC–MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis. [Copyright &y& Elsevier]

Abstract: Two series of Benzimidazole clubbed with triazolo-thiadiazoles (5a–q, 5r, 5s and 5x–a 1 ) and triazolo-thiadiazines (5t–w) were synthesized with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were investigated at the National Cancer Institute (NCI) against NCI 60 cell line panel; results showed good to remarkable broad-spectrum anticancer activity. Among them, the compound 5h (NCS: 760452, 1-(1H-benzo [d] imidazol-2-yl)-3-(6-(2,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl) propan-1-one) exhibited significant growth inhibition with GI50 values ranging from 0.20 to 2.58 μM and found superior selectivity for the leukemia cell lines and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM). The 5h may possibly be used as lead compound for developing new anticancer agents. [Copyright &y& Elsevier]

Abstract: Two new series of benzimidazole bearing oxadiazole[1-(1H-benzo[d]imidazol-2-yl)-3-(5-substituted-1,3,4-oxadiazol-2-yl)propan-1-ones (4a–l)] and triazolo-thiadiazoles[1-(1H-benzo[d]imidazol-2-yl)-3-(6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one (7a–e)] have been synthesized successfully from4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were screened at the National Cancer Institute (NCI), USA, according to their applied protocol against full NCI 60 human cell lines panel; results showed good to remarkable anticancer activity. Among them, compound (4j, NCS: 761980) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100μM) with GI50 values ranging from 0.49 to 48.0μM and found superior for the non-small cell lung cancer cell lines like HOP-92 (GI50 0.49, TGI 19.9,LC50 >100 and Log10GI50 −6.30, Log10TGI −4.70, Log10LC50 >−4.00). [Copyright &y& Elsevier]

Abstract: Starting from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (1), twenty new 1-(1H-benzo[d]imidazol-2-yl)-3-(1,3,4-oxadiazol-5-substituted derivatives-2-yl)propan-1-ones (1b–A 7 – 26 ) were synthesized under microwave irradiation in good yields. Further, compound 1b–A 7 was reacted with different secondary amines under microwave irradiation to produce five novel 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(methyl substituted)-1,3,4-oxadiazol-2-yl)propan-1-ones (1b–A 7a – e ). The title compounds were screened for their in vitro anticancer activity at National Cancer Institute (NCI), USA; at a single dose (10 μM) in NCI 60 cell line panel and results showed significant to good anticancer activity. One compound, 1b–A 18 (NSC: 759205), 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(2,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl)propan-1-one, emerged as lead compound; it was selected for five-dose level screening and found to have significant growth inhibition activity. [Copyright &y& Elsevier]

Abstract: Small punch test technique on circular shape of diminutive specimen is considered in the present study. The small punch tests are conducted on diminutive specimen of circular shaped. Four different steels are chosen for this purpose. The load on diminutive samples is quasi-statically applied using different tip diameters hemispherical headed indenter. The experimental outputs of small punch (SP) test on diminutive specimen are obtained in the form breakaway loads, load vs. displacement curve/data and reduced thickness of tested diminutive samples is measured at failure. The resulted SP experimental data are analyzed used to establish the empirical relations to predict the mechanical behaviour of materials. For this purpose, the empirical correlations are proposed for the estimation of the yield stress ductility (fracture strain) and fracture toughness and are used to predict the behaviour of four different materials under study. The standard tensile and fracture toughness tests are also carried out for comparison. The small punch test on diminutive specimen is demonstrating the strong potential for the determination of mechanical behaviour. [Copyright &y& Elsevier]

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: Synthesis and biological evaluation of various aroylpropionic acid derivatives containing 1,3,4-Oxadiazole nucleus is reported here. The compounds (3a–w) were synthesized by cyclization of 3-aroylpropionic acids into 1,3,4-oxadiazole nucleus by treating with various aryl acid hydrazides in the presence of POCl3. The structures of new compounds are supported by IR, 1H NMR and MS data. These compounds were tested in vivo for their anti-inflammatory activity. All the compounds tested showed anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. Seven (3c, g, i, j, m, o, p) out of 23 new compounds showed very good anti-inflammatory activity in the carrageenan-induced rat paw edema test with very less ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA), which is one of the byproducts of lipid peroxidation. Compound 3i and o showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid induced writhings and 0.7 and 0.65 of severity index respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen. The study showed that the cyclization of carboxylic group of aroylpropionic acids into an oxadiazole nucleus resulted in compounds having good anti-inflammatory and analgesic effects with reduced gastric irritation. [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]

This paper contains the description of an experimental and a computational study of small punch test using circular disk shaped miniature specimen, through inverse finite element procedure. An inverse finite element procedure is developed and clubbed with ABAQUS computer code for the determination of constitutive tensile behavior of materials. The proposed inverse technique is based on the small punch experimental load vs. displacement curve. Small punch tests (SPT) are conducted on circular disk shaped specimen (10 mm diameter, 0.5 mm thick) made from three different steels. By using the output of experimental small punch test, constitutive stress–strain curves are traced through inverse technique. The computed constitutive stress–strain curves are compared with the curves obtained from a standard conventional tensile test and the results obtained for all the three cases demonstrate the effectiveness of the present inverse procedure. [Copyright &y& Elsevier]

B-cell receptor (BCR) activation is a pivotal step in the progression of B-cell cancer. BCR signaling requires Bruton's tyrosine kinase (BTK). Ibrutinib (PCI-32765) is a small medication that covalently and permanently inhibits BTK. BTK's defining properties are its high potency and selectivity. The FDA and EMA have authorized ibrutinib for the second-line therapy for Mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) individuals who have had a minimum of one previous anti-CD20 (cluster of differentiate 20) based drug. It has been authorized by the FDA and the EMA for the management of Wald Enstrom's Patients with macroglobulinemia who have already had therapy or are unsuitable for immunochemotherapy. Ibrutinib nano formulations include nanoparticles composed of chitosan (CS) and sulfobutylether (SBE) ether-b-cyclodextrin that have been packed with the medication ibrutinib. Because of the inclusion of cyclodextrin, Nanoparticles have a high loading efficiency for the hydrophobic drug. Other nano versions of ibrutinib are also available, which improves Ibrutinib bioavailability. In addition, we combined clinical outcomes and side effects induced by ibrutinib in patients from several clinical and preclinical trials in one study. [Display omitted] • In B-cell receptor (BCR) signaling, Bruton's tyrosine kinase (BTK) plays key role. • Ibrutinib (PCI-32765) is a tiny drug that inhibits BTK covalently and irreversibly. • Great potency and great selectivity for BTK is its distinguishing features. • Various nanoformulations, pre-clinical & clinical findings have also been discussed. [ABSTRACT FROM AUTHOR]

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]

Nineteen novel piperine based triazoles have been synthesized using click chemistry approach and were tested for in vivo anti-inflammatory activity. The most active compounds were evaluated for in vitro TNF-α expression. Compounds 3g and 3f were found to show significant in vivo inhibition of inflammation, 80.40% and 76.71% , respectively after 5 h in comparison to piperine ( 54.72 %) and the standard drug indomethacin ( 77.02 %) without causing any damage to the stomach. Compounds 3g and 3f suppressed TNF-α level by 73.73% and 70.64% , respectively and protein expression of COX-2, NF–κB and TNF-α more than indomethacin. Moreover, the compound 3g was found to show significant analgesic activity of 54.09% which was comparable with the indomethacin ( 57.43% ). [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]

Abstract: A number of 6-(substituted phenyl)-2-(4-substituted phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydropyridazin-3(2H)-one derivatives were designed and synthesized by a sequence of reactions starting from respective aryl hydrocarbons. The final compounds (4a–4u) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 4e, 4i and 4k showed appreciable antihypertensive activity comparable with that of standard hydralazine and propranolol. [ABSTRACT FROM AUTHOR]