DESIGN AND SYNTHESIS OF NOVEL 1-((DIMETHYLAMINO)METHYL)-3-(4-(3-(SUBSTITUTE DPHENYL)-4-OXOTHIAZOLIDIN-2-YL)PHENYLIMINO)-5-NITROINDOLIN-2-ONES AS POTENT ANTITUBERCULAR AGENTS

Objective: Isatins have emerged as antimicrobial agents due to their broad spectrum of in vitro and in vivo antimicrobial activities. In addition, thiazolidinone also reported to possess various biological activities particularly antimicrobial activity. Due to the importance, we planned to synthesize compounds with isatin functionality coupled with thiazolidinone as possible antitubercular and antimicrobial agents which could furnish better therapeutic results. Methods: In vitro Mycobacterium tuberculosis method and agar streak dilution test are used to estimate antitubercular and antimicrobial potency of title analogs, respectively. Minimum inhibitory concentration of entire title compounds was determined against all tested microorganism such as M. tuberculosis, four Gram-positive, three Gram-negative bacteria, and two fungi. Results: A series of new thiazolidinone substituted Schiff and Mannich bases of 5-nitroisatins were designed and synthesized by a multistep synthesis from isatin. Structures of synthesized compounds are characterized using Fourier-transform infrared, proton nuclear magnetic resonance, mass spectroscopy, and bases of elemental analysis. Mild to good antitubercular and antimicrobial activity was showed by synthesized 5-nitroisatin analogs. The relationship between the biological activity and the functional group variation of the tested compounds was discussed. Conclusion: 3-(4-(3-(4-Aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethyl amino)methyl)-5-nitroindolin-2-one 6 and 3-(4-(3- (2-aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethylamino)methyl)-5-nitroindolin-2-one 13 were found to be the most potent compounds of this series which might be extended as a novel class of antimicrobial agents

DEVELOPMENT AND VALIDATION OF NEW RP-UPLC METHOD FOR THE DETERMINATION OF CEFDINIR IN BULK AND DOSAGE FORM

Objective: The objective of the study was to develop and validate a new rapid and sensitive reverse phase ultra-performance liquid chromatographic (RP-UPLC) method for determination of cefdinir in bulk drug and dosage form.Methods: Separation was achieved with an Acquity SB C18 (100 × 2 mm) 1.8μm column with an isocratic mobile phase containing a mixture of orthophosphoric acid and acetonitrile (60:40 v/v) and pH adjusted to 2.8. The flow rate of the mobile phase was 0.3 ml/min with a column temperature of 30 °C and detection wavelength at 285 nm.Results: The method was validated with respect to linearity, accuracy, precision, detection limits, robustness and specificity. The precision of the results, stated as the relative standard deviation was below 1.5%. The calibration curve was linear over a concentration range from 25 to 150μg/ml with a correlation coefficient of 0.9993. The accuracy of the method demonstrated at three levels in the range of 50%, 100% and 150% of the specification limit. The recovery of cefdinir was found to be in the range of 98 to 102%, whereas the detection limits were found to be 0.17 and 0.51µg/ml. Forced degradation study was carried out under acidic, alkaline, oxidative, photolytic and thermal conditions to prove the stability-indicating ability of the developed UPLC method.Conclusion: The developed method was validated with respect to linearity, accuracy, precision limit of detection and quantification, robustness and specificity. The method was applied successfully for the determination of cefdinir in tablets

METHOD DEVELOPMENT, VALIDATION AND STABILITY STUDIES FOR DETERMINATION OF BUMETANIDE IN BULK AND PHARMACEUTICAL DOSAGE FORM BY RP-UPLC

Objective: The objective of the study was to develop a new, simple, accurate, precise and reproducible RP-UPLC method for the estimation of bumetanide in bulk and pharmaceutical dosage form.Methods: Acquity SB C18, 2 x 100 mm, 1.8 µmm, 5m particle size column with the mobile phase consisting of water: acetonitrile in the ratio of 30:70 v/v were used. The effluents were moniRTat 254 nm and the flow rate was 1.0 ml/minute.Results: The retention time was 0.852 min. Quantitative linearity was obeyed in the concentration range of 12.5 to 75 μg/ml. The correlation coefficient for bumetanide was found to be 0.999. Recovery and assay studies of bumetanide were within 99 to 102%, indicating that the proposed method can be adaptable for quality control analysis of bumetanide. The % RSD for precision and accuracy of the method was found to be less than 2%. Bumetanide was subjected to stress environment of degradation in aqueous solutions including oxidation, hydrolysis, thermal and photolysis degradation.Conclusion: Proposed method was found to be simple, accurate, precise, and quick and can be used for regular analysis. This condition was applied to tablet dosage form. The statistical parameters and recovery studies were reported

SYNTHESIS AND ANTI-EPILEPTIC ACTIVITY OF SOME NOVEL 3-(4-(4-(SUBSTITUTED BENZYLIDENEAMINO)-5-MERCAPTO-4-1,2,4-TRIAZOLE-3-YL)PHENYLIMINO)-1-((DIMETHYL AMINO) METHYL)-5-FLUOROINDOLIN-2-ONE DERIVATIVES

Objective: Synthesis and anti-epileptic evaluation of some novel Schiff and Mannich bases of isatin derivatives. Methods: A series of novel 3-(4-(4-(substituted benzylideneamino)-5-mercapto-4-1,2,4-triazole-3-yl)phenylimino)-1-((dimethyl amino) methyl)-5-fluoroindolin-2-one Schiff and Mannich base derivatives were synthesized by using various aromatic aldehydes with isatin derivatives. The chemical structures of all synthesized compounds were confirmed by IR, 1H-NMR, Mass spectra and elemental analysis. All the synthesized compounds were screened for its anti-epileptic activity by MES and scPTZ methods using Phenytoin and Ethosuximide as standards. Results: The results of anti-epileptic activity showed that some of the synthesized compounds were exhibited significant results. Conclusion: This investigation identified the potent anti-epileptic agents and these molecules will be subjected to further studies in our laboratory

SYNTHESIS, ANALGESIC, ANTI-INFLAMMATORY AND IN VITRO ANTIMICROBIAL STUDIES OF SOME NOVEL SCHIFF AND MANNICH BASE OF 5-SUBSTITUTED ISATIN DERIVATIVES

Objective: Synthesis and analgesic, anti-inflammatory and antimicrobial evaluation of some novel Schiff and Mannich bases of isatin derivatives. Methods: A series of novel 3-(4-(2-(substituted benzylideneamino)thiazol-4-yl)phenylimino)-1-((dimethylamino)methyl)-5-fluoroindolin-2-one Schiff and Mannich base derivatives were synthesized by using various aromatic aldehydes with isatin derivatives. The chemical structures of all synthesized compounds were confirmed by IR, 1H-NMR, Mass spectra and elemental analysis. All the synthesized compounds were screened for its analgesic, anti-inflammatory and antimicrobial activity. Results: The results of analgesic, anti-inflammatory and antimicrobial activity showed that some of the synthesized compounds were exhibited promising results. Conclusion: This investigation identified the potent analgesic, anti-inflammatory and anti-microbial agents and these molecules will be subjected to further studies in our laboratory

Numerical Investigation of the Intake Flow Characteristics for a Ramjet Engine with and without Heat Addition in the Combustion Chamber

The flow field in the supersonic mixed compression axisymmetric as well as two-dimensional intake have been investigated numerically. The flow characteristics, such as pressure, temperature, and velocity have been obtained. An enlarged chamber with a supersonic convergent-divergent nozzle has been integrated at the air intake exit to simulate the ramjet engine. Suitable heat addition at the inner surface of the wall has enabled the simulation of combustion chamber condition. The well-known modes of operation of the ramjet engine air intake have been predicted by the mathematical simulations. A comparative study for supercritical, critical, and subcritical -; conditions has been presented. The predicted flow features including shock locations and the static pressure distributions along the cowl, as well as the centre body are in agreement with the available experimental results in the published literature. The effect of thermal input in the combustion chamber on the flow characteristics of the air intake has been studied in detail. The characteristic curve of generic supersonic air intake can be obtained through these numerical studies

Numerical Modelling of Liquid Ramjet Combustors

The liquid fuel ramjet system employing a subsonic side-dump combustor is simulated inthe present study, and the predictions are compared with the available experimental data. Thecomplex combustion phenomenon in a ramjet combustor has been carried out using probabilitydensity function (PDF)  approach. The complexity arises because of the mixing of fuel and airstreams, and the burning of the resultant mixture, within the confined space of the combustionchamber. The predicted numerical results have been validated with the results available in openliterature for a two-dimensional case and with in-house experimental data for a three-dimensionalcase. The methodology allows different designs to be evaluated quantitatively based on theperformance metrics such as combustion efficiency, flame stability, etc.Defence Science Journal, 2008, 58(1), pp.3-14, DOI:http://dx.doi.org/10.14429/dsj.58.162

Numerical Analysis of Integrated Liquid Ramjet Engine

The numerical simulation of an integrated, liquid-fuelled ramjet engine comprising supersonicair intake, subsonic combustor and a convergent-divergent nozzle has been carried out and theresults are discussed in this paper. These results include cold flow studies, heat addition in thecombustor and full engine analysis with coupled simulation of supersonic air-intake andcombustion chamber along with the nozzle. Overall ramjet operation depends on the performanceof the air intake and the combustion chamber.  The coupling phenomena are very dominant andperformance of air intake is affected vastly by the combustor operation and vice versa. In thispaper, a numerical analysis of integrated liquid ramjet engine considering coupling phenomenabetween various sub-systems viz., air intake, combustor and nozzle has been reported

Identification of phenolic constituents of cytisus multiflorus

The phenolic composition of the ethanolic extract obtained from the flowers of the medicinal plant Cytisus multiflorus has been elucidated by high performance liquid chromatography, electrospray mass spectrometry and nuclear magnetic resonance analysis. The extract was mainly composed of flavones, including the common chrysin, orientin, luteolin-5-O-glucoside, luteolin-7-O-glucoside, apigenin and apigenin-7-O-glucoside, which appeared as minor components. The major flavone in the extract was chrysin-7-O-B-D-glucopyranoside, and it also contained moderate amounts of a dihydroxyflavone isomer of chrysin, as well as of 2''-O-pentosyl-6-C-hexosyl-luteolin, 2''-O-pentosyl-8-C-hexosyl-luteolin and 6''- O-(3-hydroxy-3-methylglutaroyl)-2''-O-pentosyl-C-hexosyl-apigenin, which are not commonly found in the Fabaceae family. Other novel phenolic compounds found in the ethanolic extract of C. multiflorus comprised the flavones 2''-O-pentosyl-6-C-hexosyl-apigenin, 2''-O-pentosyl-8-C-hexosyl-apigenin and 6''-O-(3-hydroxy-3-methylglutaroyl)-200-O-pentosyl-C-hexosyl-luteolin. The assessment of the biological activities of the main compounds of this extract are now keen, in order to determine their relevance in the beneficial properties of the plant

Evaluation of behavioural and antioxidant activity of Cytisus scoparius Link in rats exposed to chronic unpredictable mild stress

<p>Abstract</p> <p>Background</p> <p>Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. <it>Cytisus scoparius </it>(CS) Link, (Family: Leguminosae), also called <it>Sarothamnus scoparius</it>, has been shown in <it>invitro </it>experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats.</p> <p>Methods</p> <p>60% methanolic extract of CS was quantified for phenolic content by Folin-Ciocalteau's method. Chronic unpredictable mild stress (CMS) was employed to induce stress in rats. CS (125 and 250 mg/kg, p.o) and diazepam (DZM) (2 mg/kg, p.o) was administered during the 21 day stress exposure period. Anxiolytic and antidepressant activities of CS were assessed in open field exploratory and behavioural despair paradigms, respectively. Plasma glucose and total lipids; endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT); non-enzymic-ascorbic acid and thiobarbituric acid reactive substances (TBARS) levels were measured in brain, kidneys and adrenals using standard protocols to assess the effect of CS.</p> <p>Results</p> <p>Total phenolic content of CS was found to be 8.54 ± 0.16% w/w. CMS produced anxiogenic and depressive behaviour in experimental rats with metabolic disturbance. Significant decrease in SOD, CAT levels and increase in lipid peroxidation level was observed in stressed rats. CS administration for 21 days during stress exposure significantly increased the ambulatory behaviour and decreased the freezing time in open field behaviour. In behavioural despair test no significant alteration in the immobility period was observed. CS also improved SOD, CAT, and ascorbic acid level and controlled the lipid peroxidation in different tissues.</p> <p>Conclusion</p> <p>CS possesses anti-stress and moderate anxiolytic activity which may be due, in part, to its antioxidant effect that might warrant further studies.</p