Synthesis and goat pulmonary vasodilatory activity of some novel 1,3,4-oxadiazoles

AbstractA novel series of[(1Z)-1-(2,2-disubstituted-5-pyridin-4-yl-1,3,4-oxadiazol-3(2H)-yl) ethylidene] (PSMB1–PSMB15) were synthesized as title compounds. The synthesis route included the cyclization of carbonyl hydrazone in the presence of excess of acetic anhydride and subsequent condensation with various aromatic amines. All the title compounds were characterized by IR, 1H NMR, MS and elemental analysis. They were screened for their goat pulmonary vein relaxant activity. Compound PSMB9 was found the most active derivative exhibiting 83.33% relaxation. Isosorbide dinitrate was used as the standard drug for goat pulmonary vein relaxant activity

Synthesis and anti-inflammatory activity of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide

A novel compounds of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide (PJS1-PJS6) were synthesized by condensation of niflumic acid with aromatic amines using most reactive Lewis reagent: polyphosphoric acid trimethyl silyl ester (PPSE). These compounds were characterized by IR, 1H-NMR, HRMS-FAB and elemental analysis and evaluated for anti-inflammatory activity using carrageenin- induced rat paw oedema method. Compound PJS 5 showed significant activity exhibiting comparable reduction in edema.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis and anti-inflammatory activity of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide

A novel compounds of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide (PJS1-PJS6) were synthesized by condensation of niflumic acid with aromatic amines using most reactive Lewis reagent: polyphosphoric acid trimethyl silyl ester (PPSE). These compounds were characterized by IR, 1H-NMR, HRMS-FAB and elemental analysis and evaluated for anti-inflammatory activity using carrageenin- induced rat paw oedema method. Compound PJS 5 showed significant activity exhibiting comparable reduction in edema.Colegio de Farmacéuticos de la Provincia de Buenos Aire

2D and 3D QSAR studies and antibacterial activity of 4-methyl-3-(6-{[arylmethylene] amino}pyridin-3-YL)-2H-chromen-2-one derivatives

4-methyl-3-(6-{[arylmethylene] amino} pyridin-3-yl)-2H-chromen-2-one derivatives containing different functional groups have been synthesized and screened for their antibacterial activity against four different strains of bacteria. 2D and 3D QSAR analysis of synthesized derivatives were performed on Vlife MDS 3.5 software. The data set for QSAR studies encompassed activities of 64 molecules divided into training and test set. The best models were selected on basis of correlation coefficient (r2) and internal and external predictivity (Pred_r2) of the QSAR model. QSAR models reveled that electronic, steric and liphophillic parameters have correlation with antibacterial activity. The 3D interactions and their contributions indicate multi-targeted mode of action of the compounds.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis, Characterization and Quantification of Simvastatin Metabolites and Impurities

Simvastatin is used in treatment of hypercholesterolemia because it regulates cholesterol synthesis as a result of its β-hydroxy acid acting as an inhibitor of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA). The present communication deals with synthesis, characterization and development of accurate, precise and sensitive Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for simultaneous estimation of simvastatin and its synthetic impurities. The impurities methyl ether and β-hydroxy acid of simvastatin were synthesized in the laboratory and characterized by MS, NMR and FT-IR spectroscopy. The separation of simvastatin and its impurities was carried out on an isocratic JASCO RP-HPLC system using KYA TECH HIQ SIL C18 column (150 × 4.6 mm internal diameter, particle size 5 μm) operating at ambient temperature using acetonitrile:water (80:20 v/v) with 0.1% orthophosphoric acid as mobile phase. The method developed for HPLC analysis of three impurities along with simvastatin was validated using ICH Q2B (R1) guidelines and it complied with these guidelines. The results of analysis were found to be in the range of 98.14% to 101.89% for all analytes with acceptable accuracy and precision. The method can be used for detection and quantification of synthetic impurities in bulk or formulations of simvastatin

Synthesis, characterization and evaluation of the effect of chemical modification of chitosan on drug release

A novel polymer, chemically modified chitosan was synthesized by reacting with hydrochloride salt of 2-aminoethanoyl chloride. Formation of novel chemically modified chitosan was confirmed by FTIR and NMR spectroscopy and by thermal (DSC) and elemental analysis. Acute oral toxicity study was performed on modified chitosan to check its safety. Ibuprofen, paracetamol and diclofenac sodium tablets were compressed on a single punch tablet machine using the weight granulation method. The drug release was found to be delayed from the formulations containing chemically modified chitosan. Thus, it could be concluded that the change in the hydrophilic balance and the resultant change in the modulation of swelling of the polymer may retard the drug release from polymer matrices.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis and anti-inflammatory activity of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide

A novel compounds of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide (PJS1-PJS6) were synthesized by condensation of niflumic acid with aromatic amines using most reactive Lewis reagent: polyphosphoric acid trimethyl silyl ester (PPSE). These compounds were characterized by IR, 1H-NMR, HRMS-FAB and elemental analysis and evaluated for anti-inflammatory activity using carrageenin- induced rat paw oedema method. Compound PJS 5 showed significant activity exhibiting comparable reduction in edema.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Novel Spectrophotometric Method for Estimation of Olmesartan Medoxomil from its Tablet Dosage Form Using Hydrotropic Solubilization

Aim: Quantitative estimation of poorly water-soluble drugs involves use of organic solvents. In the present investigation, hydrotropic solubilization is employed to enhance the aqueous solubilities of poorly water-soluble drugs like Olmesartan Medoxomil in tablet dosage forms. Material and methods: This method utilizes 0.05 M Sodium acetate solution as hydrotropic solubilizing agent Where Olmesartan Medoxomil shows maximum absorbance at 256 nm. The 0.05 M Sodium acetate solution does not show any interference with the sampling wavelength. The hydrotropic agent and additives used in the manufacture of tablets did not interfere in the analysis. Results and Conclusion: The drug obeys the Beer’s Law in the concentration range 2-14 μg/ml with correlation coefficient value of 0.9987. The developed reliable method was validated statistically following ICH Q2B (R1) guidelines. Statistical analysis proved that the method was simple and rapid for the estimation of Olmesartan Medoxomil and can be used for routine analysis of Olmesartan Medoxomil in quality control laboratories. The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 Kg.m.s-2. The in vitro drug release studies revealed that formulation FA8 released 84% and FB16 released 99.01% of drug in 140 min.Objetivo: La estimación cuantitativa de fármacos poco solubles en agua implica el uso de disolventes orgánicos. En la presente investigación, se emplea la solubilización hidrotrópica para mejorar las solubilidades acuosas fármacos poco solubles en agua como el olmesartán medoxomilo dosificado en comprimido. Material y Métodos: Este método emplea acetato sódico 0,05 M como agente solubilizante hidrotrópico, mostrando el olmesartán medoxomilo una absorbancia máxima a 256 nm. La solución de acetato 0.05 M no muestra ninguna interferencia con la longitud de onda de muestreo. El agente hidrotrópico y los aditivos utilizados en la elaboración de los comprimidos no interfieren en el análisis. Resultados y conclusiones: El fármaco obedece a la Ley de Beer en el intervalo de concentraciones 2-14 mg / ml con un de coeficiente de correlación de 0,9987. El método desarrollado fue validado estadísticamente siguiendo las directrices ICH Q2B (R1) . El análisis estadístico demostró que el método era sencillo y rápido para la estimación de olmesartán medoxomilo y se puede utilizar para análisis de rutina de olmesartán medoxomilo en laboratorios de control de calidad

HPLC ANALYSIS OF HUMAN URINE FOR OXALATE CONTENT

Objective: In the present communication, development and validation of reverse phase-high performance liquid chromatography method have been carried out for estimation of oxalate content in the urine of human volunteers with recurrent kidney stone disease and healthy status.Methods: The analysis of oxalic acid has been carried out on KYA TECH HiQ Sil C18HS column using a mobile phase of methanol: 0.001 N acetic acid in water (50:50, v/v) with a flow rate of 1 ml/min and detection wavelength, 237 nm.Results: Analysis of oxalate content was carried out using single point calibration method with retention at 2.705 min with good resolution parameters. Urine sample collected from kidney stone patients and healthy volunteers over the period of 24 h were analyzed and it has been found that concentration of oxalate in healthy volunteers is less than 12 µg/ml whereas that in case of kidney stone patients is in the range of 39-151 µg/ml and this data can be utilized for further interpretations about oxalate content in healthy and kidney stone diseased volunteers. This method was validated as per united states food and drug administration (USFDA) guidelines by the study of accuracy, precision, linearity, range, selectivity, the lower limit of quantitation, extraction recovery studies and stability studies for determining oxalate content in the urine of human volunteers. As relative standard deviations of oxalate content estimated are less than 5 percent, the method can be claimed accurate, precise, sensitive and selective for determining oxalate content in the urine of human volunteers.Conclusion: The results are satisfactory, proving the effectiveness of the method for analysis of oxalate content from other biological fluids with few optimizations

2 D QSAR and docking of novel N-substitutedAryl amine derivatives as potential inhibitors of lumazine synthase

Fungi play a predominant role in microbial infections with serious health risk to immunocompromised individuals, including AIDS, cancer, diabetics, newborns and elderly patients. Fungi specific riboflavin metabolism involves lumazine synthase catalyzed synthesis of 6,7-dimethyl-8-D-ribityl lumazine which is converted to riboflavin by a riboflavin synthase. Therefore lumazine synthase has been targeted for design of newer antifungal agents. 32 novel N-substituted aryl amine derivatives have been designed, synthesized, characterized and screened as antifungals. Molecular modelling and docking studies with fungal lumazine synthase using the 32 inhibitors have elucidated unique binding areas within the active site of the enzyme. Amongst the selected 2-D QSAR descriptors, chiV3Cluster and Most +ve Potential show positive correlation with antifungal activity while XX Polarizability, XY Polarizability, Heat of Formation and Quadruple 3 show negative correlation with antifungal activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire