SIMPLE AND RAPID HPLC METHOD DETERMINATION OF CSR1 AND CSR2, NEW HETEROCYCLIC THIAZOLIDINEDIONE DERIVATIVES, IN RAT PLASMA

Objective: This study aimed at developing a simple and rapid high-performance liquid chromatography (HPLC) method for determination of two thiazolidinedione derivatives, which were developed as anti-proliferative moieties (CSR1 and CSR2) in rat plasma. In addition, their oral pharmacokinetics were studied.Methods: Drugs were recovered from plasma using acetonitrile and analyzed on a Kromasil C8 column (250 mm × 4.6 mm; 4 μm). HPLC running conditions (0.01M phosphate buffer [pH = 3.0]; flow rate, 0.9 ml/min; at 210 nm; run time, 17 min) were optimized and further used for the determination of pharmacokinetic parameters.Results: At the described chromatographic conditions, CSR1, CSR2 and internal standard (metformin) eluted at 10.44, 9.41, and 3.15 min, respectively. The calibration curves were linear over the range of 0.25–20 µg/ml, with a correlation coefficient>0.999. The quantification limit was 0.25 µg/ml. Within- and between-day precision values were less than 15%. The developed HPLC method was successfully used to study the pharmacokinetics of CSR1 and CSR2 in rats. The developed method was successfully used to study the pharmacokinetics of CSR1 and CSR2. Cmax, AUC0-12, Tmax, t1/2 for CSR1 were 12.2±1.9 µg/ml, 65.34±0.12 µg h/ml, 4.07±0.23 h, t1/2= 4.54±0.12 h, respectively, and those for CSR2 were 10.6±2.2 µg/ml, 62.45±0.31 µg h/ml, 3.56±0.23 h, 3.86±0.09 h, respectively.Conclusion: A specific, linear, and reproducible method was successfully developed and implemented to determine pharmacokinetic activity for two thiazolidinedione derivatives (CSR1 and CSR2), which have been shown to have significant anti-proliferative activity.Â

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS OF NOVEL PYRAZOLINE DERIVATIVES USING K NEAREST NEIGHBOUR MOLECULAR FIELD ANALYSIS METHOD

Objective: Malonyl CoA decarboxylase (MCD) enzyme plays important role in fatty acid and glucose oxidation. Inhibition of MCD might turn to a novel approach to treat ischemia. The main objective of this research article was to develop a novel pharmacophore for enhanced activity.Methods: Three-dimensional quantitative structure-activity relationships (3D-QSAR) was performed for pyrazoline derivatives as MCD inhibitors using VLife MDS 4.6 software. The QSAR model was developed using the stepwise 3D-QSAR kNN-MFA method.Results: The statistical results generated from kNN-MFA method indicated the significance and requirements for better MCD inhibitory activity. The information rendered by 3D-QSAR model may render to better understanding and designing of novel MCD inhibitors.Conclusion: 3D-QSAR is an important tool in understanding the structural requirements for the design of novel and potent MCD inhibitors. It can be employed to design new drug discovery

Computer-assisted design of novel leukotriene C4 receptor antagonists

1160-116

Ester prodrugs of flurbiprofen: Synthesis, plasma hydrolysis and gastrointestinal toxicity

1164-1168Nine alkyl ester prodrugs of flurbiprofen have been synthesized with an aim to reduce it’s gastrointestinal side-effects. The synthesized prodrugs have been subjected to plasma hydrolysis and gastrointestinal toxicity studies. The chemical structures of the prodrugs have been varied in terms of lipophilicity and reactivity towards hydrolysis. The plasma hydrolysis studies indicate that methyl and propyl prodrugs of flurbiprofen undergo faster hydrolysis as compared to the remaining ester prodrugs. Reduction of ulcer index in rats indicate that n-propyl, iso-propyl, benzyl and cyclopentyl prodrugs of flurbiprofen are significantly (p< 0.05) less irritating to the gastric mucosa as compared to the parent drug, i.e., flurbiprofen

Synthesis and anti-inflammatory activity of fluorinated chalcone derivatives

2064-2067A series of twelve 2',4'-difluorinated chalcones have been synthesized by Claisen-Schmidt condensation of 2',4'-difluoroacetophenone with appropriately substituted benzaldehydes. These compounds have then been subjected to preliminary anti-inflammatory screening using the carrageenan induced rat paw oedema model. Compounds 1, 7, 10 and 11 have activity comparable to indomethacin at 20 mg kg⁻¹ by oral route

Synthesis and anti-inflammatory activity of fluorinated propanedione derivatives

364-367A new series of five 1-(2′,4′-difluorophenyl)-3-(substituted phenyl)-1,3 propanediones from 2′,4′-difluorinated chalcones have been synthesized. All the compounds (20 mg/kg po) possess anti-inflammatory activity, as reflected by their ability to provide protection (70.00 - 93.00%) against carrageenan induced edema in rat paw. Standard indomethacin provided 79.00% protection at the same dose. The safety of these substituted propanediones are reflected by toxicity studies

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS OF NOVEL PYRAZOLINE DERIVATIVES USING K NEAREST NEIGHBOUR MOLECULAR FIELD ANALYSIS METHOD

Objective: Malonyl CoA decarboxylase (MCD) enzyme plays important role in fatty acid and glucose oxidation. Inhibition of MCD might turn to a novel approach to treat ischemia. The main objective of this research article was to develop a novel pharmacophore for enhanced activity.Methods: Three-dimensional quantitative structure-activity relationships (3D-QSAR) was performed for pyrazoline derivatives as MCD inhibitors using VLife MDS 4.6 software. The QSAR model was developed using the stepwise 3D-QSAR kNN-MFA method.Results: The statistical results generated from kNN-MFA method indicated the significance and requirements for better MCD inhibitory activity. The information rendered by 3D-QSAR model may render to better understanding and designing of novel MCD inhibitors.Conclusion: 3D-QSAR is an important tool in understanding the structural requirements for the design of novel and potent MCD inhibitors. It can be employed to design new drug discovery

Dyslexia: Symbol processing difficulty in the Kannada language

The purpose of this study was to investigate whether among children who speak Kannada, a Dravidian language from South India, there are those who show the same pattern of specific dyslexia as has been found to occur in children who speak European languages. The performances of 14 dyslexic children, aged between 8 and 10 years, whose native language was Kannada, were compared on a variety of tasks with fourteen normal readers and fourteen non-dyslexic poor readers. There were no significant differences between the three groups on tests of visual discrimination, visual recognition, visual recall, memory for shapes in sequence, or auditory discrimination. There were differences. however, between the dyslexics and the normal readers on tests of recall of auditorily presented digits, word analysis, word synthesis, and on two tests of visual-verbal association. The non-dyslexic poor readers were more similar to the dyslexics on recall of auditorily presented digits and word synthesis but more similar to the normal readers on word analysis and on the two tests of visual-verbal association. It is argued that these results are evidence of a consistent pattern in specific dyslexia which does not depend on any one writing system or geographical location

Development and Validation of a UPLC-MS/MS Assay for Simultaneous Estimation of Raloxifene and its Metabolites in Human Plasma

International audienceAn aim of the study is development and validation of a method for the simultaneous estimation of raloxifene (RAL) and its two active metabolites, raloxifene-4-glucuronide (R4G) and raloxifene-6-glucuronide (R6G) in human plasma samples using raloxifene-D4 as an Internal Standard. Sample preparation was performed by solid phase extraction (SPE) and was followed by separation of the analytes on a UPLC system with a linear gradient and a mobile phase consisting of acetonitrile and ammonium formate. Detection was achieved by tandem mass spectrometry operated in the electrospray positive ion mode. The method had a short sample preparation time, as well as a chromatographic run time of just 4.2 min, the shortest so far reported for RAL, R4G and R6G determination. It was validated and fulfilled all preset criteria for sensitivity, specificity, linearity, within inter-and intra-accuracy and precision, stability studies for all molecules. The method was linear in the concentration range of 0.040 to 1.5 ng/mL, 0.6 to 50.0 ng/mL and 0.6 to 50.0 ng/mL for RAL, R4G and R6G, respectively. The proposed method could be applied to the rapid and reliable simultaneous determination of RAL, R4G and R6G in a bioequivalence study