Sudheer Moorkoth

Anti-arthritic potential of the plant Justicia gendarussa Burm F

OBJECTIVE: To evaluate the anti-arthritic potential of the plant Justicia gendarussa using two different rat models. MATERIALS AND METHOD: The anti-arthritic potential of the alcoholic extract of the plant Justicia gendarussa was evaluated using the Freund’s adjuvant-induced and collagen-induced arthritic rat models. The rats were treated with the ethanolic extract of Justicia gendarussa and with standard aspirin. RESULTS: The ethanolic extract of Justicia gendarussa showed significant anti-arthritic activity that was statistically similar to that of aspirin. Our results suggest that the alcoholic extract of Justicia gendarussa exhibits significant anti-arthritic potential.

Evaluation of Chemical Interactions of Maleic acid with Sodium Hypochlorite and Chlorhexidine gluconate

INTRODUCTION The elimination of microorganisms from the root canal system necessitates the use of combination of irrigating solutions to enhance their antimicrobial property. The combination of irrigants and their interaction sometimes could be detrimental to the outcome of the root canal therapy. The purposes of this study were (1) to evaluate the interaction between 7% maleic acid (MA) and 2% chlorhexidine gluconate solution (CHX) and to find out the availability of individual irrigant and (2) to determine the free available chlorine content when 7% MA was mixed with 2.5% sodium hypochlorite (NaOCl) solution. METHODS Interaction between MA and CHX was assessed by high-performance liquid chromatography. Available chlorine content in NaOCl was evaluated by the standard iodine/thiosulfate titration method. RESULTS It was observed that more than 90% free MA and CHX were available when MA was combined with CHX. It was also observed that there was no precipitate formation when 7% MA was mixed with 2% CHX. Available chlorine content decreased significantly in the MA/NaOCl mixture. CONCLUSIONS There were no adverse interactions or precipitate formation observed when MA was combined with CHX, but the available chlorine content was reduced when NaOCl was mixed with MA.

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones

Abstract A series of novel 5-alkyl/aryl thiadiazole substituted thiazolidin-4-ones were synthesized by a two-step process. In the first step, 5-alkyl/aryl substituted 2-aminothiadiazoles were synthesized, which on reaction with substituted aromatic aldehydes and thioglycolic acid in the presence of dicyclohexylcarbodiimide afforded thiazolidin- 4-ones. All the compounds were synthesized in fairly good yields and their structures were confirmed by spectral and physical data. The title compounds were screened for in vitro anti-proliferative activity on human breast adenocarcinoma cells (MCF-7) by MTT assay. Most of the derivatives showed an IC50 less than 150 μmol L-1. Among the compounds tested, 2-(2-nitrophenyl)- 3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3f), 2-(3-fluorophenyl)-3-(5-methyl-1,3,4-thiadiazol-2- -yl)-thiazolidin-4-one (3b), and 2-(4-chlorophenyl)-3- -(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3c) were found to be the most active derivatives with IC50 values of 46.34, 66.84, and 60.71 μmol L-1, respectively. Antioxidant studies of all the synthesized compounds were carried out by diphenylpicrylhydrazyl (DPPH) assay. Among the compounds tested, 2-phenyl-3-(5-styryl- -1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3s) elicited superior antioxidant activity with IC50 of 161.93 μmol L-1.

Comparing the anti-arthritic activities of the plants Justicia gendarussa Burm F and Withania somnifera Linn

The aim of this study was to compare the anti-arthritic activities of the plants Justicia gendarussa and Withania somnifera. Arthritis is induced in male albino rats using Freund’s complete adjuvant and bovine type II collagen. Leaves of J. gendarussa and roots of W. somnifera were powdered and extracted with ethanol (95%) using the soxhlet method. The effect of these plant extracts on arthritic rats were assessed by various blood parameters and also by taking the change in paw volume. The plants J. gendarussa and W. somnifera suppressed the anti-arthritic changes induced in rats and the results were statistically significant. Key words: Arthritis, collagen, paw volume, plant extract

Synthesis and evaluation of a series of novel imidazolidinone analogues of 6-aminoflavone as anticancer and anti-inflammatory agents

The flavone moiety is a potential pharmacophore known for its diverse range of pharmacological activities. Aminoflavones have recently been the subject of considerable attention as lead molecules in several cancer research projects. Imidazolidinone heterocycles represent another biologically active scaffold with known cytotoxic properties. In an attempt to provide synergistic cytotoxic activity, these two moieties have been combined, and the resulting novel analogues evaluated for their anticancer and anti-inflammatory activities. The results revealed that the cytotoxicities of these compounds were fivefold greater than those of aminoflavone. DNA histograms obtained from cell cycle analysis in the presence of these compounds were apoptotic in their nature. Furthermore, the in vivo screening of these compounds using Ehrlich’s ascites tumour model showed an increase in life span, whereas an in vivo anti-inflammatory study resulted in the enhancement of the anti-inflammatory potential. The results therefore supported the hypothesis that there is a relationship between inflammation and cancer.

Development and Validation of GC-MS Bioanalytical Method to Detect Organic Acidemia in Neonatal/Pediatric Urine Samples

This work was aimed at developing an analytical tool for the simultaneous quantification of methylmalonic acid, glutaric acid, succinyl acetone, homogentisic acid, and pipecolic acid in pediatric urine samples. Organic acids were isolated from urine by liquid-liquid extraction. The extracted samples were then derivatized by using BSTFA + 1% TMCS solution, which resulted in the formation of trimethylsilyl ester derivatives. These analytes were quantified by GC-MS, and this bioanalytical method was validated according to the USFDA guidelines. The proposed method was applied to several clinically suspected organic acidemia samples. The linearity range is within 5 – 100 μg/mL for methylmalonic acid and glutaric acid, 20 – 100 μg/mL for succinyl acetone and homogentisic acid, and 10 – 100 μg/mL for pipecolic acid. Mean % recovery of QC samples of methylmalonic acid, glutaric acid, succinyl acetone, homogentisic acid, and pipecolic acid was found to be 92.06, 92.21, 90.92, 93.17, 90.71%, respectively, and that of tropic acid was 96.57%. All organic acids were stable at room temperature for 8 h. The stability of succinyl acetone, homogentisic acid, and pipecolic acid stored for 30 days at 8°C was found to be lower. The proposed method was applied to the analysis of samples obtained from 23 patients.

Biomarker Profiling for Pyridoxine Dependent Epilepsy in Dried Blood Spots by HILIC-ESI-MS

Pyridoxine dependent epilepsy is a condition where the affected infant or child has prolonged seizures (status epilepticus), which are nonresponsive to anticonvulsant therapy but can be treated with pharmacological doses of pyridoxine. If identified earlier and treated prophylactically with pyridoxine, severe brain damage due to seizures can be prevented. Alpha-amino adipic semialdehyde (AASA), piperidine-6-carboxylic acid (P6C), and pipecolic acid (PA) are known biomarkers of pyridoxine dependent epilepsy. We report the development and validation of a hydrophilic interaction liquid chromatography (HILIC) hyphenated with mass spectroscopy for the quantification of the above analytes from dried blood spot samples. The samples were extracted using methanol and analysed on a iHILIC fusion plus column with formic acid buffer (pH 2.5): acetonitrile (20:80) at a flow rate of 0.5 mL/min within 3 minutes. The method demonstrated a LOD of 10 ng/mL, LOQ of 50 ng/mL, linearity of r2 ≥ 0.990, and recovery of 92-101.98% for all analytes. The intra- and interday precision CVs were < 8% and 6%, respectively. Extensive stability studies demonstrated that the analytes were stable in stock solution and in matrix when stored at -80°C. We performed method comparison studies of the developed method with the literature reported method using normal samples and matrix matched spiked samples at pathological concentrations to mimic clinical validity. The Bland-Altman analysis for comparison of the analytical suitability of the method for the biomarkers in healthy and spiked samples with the literature reported method revealed a bias which suggested that the method was comparable. The newly developed method involves no derivatisation and has a simple sample preparation and a low run time enabling it to be easily automated with a high sample throughput in a cost-effective manner.

Analytical Method Development and Validation of RP-HPLC Method for Simultaneous Estimation of N-acetyl cysteine and Cefexime from its Fixed Dose Combination

A simple novel validated isocratic reverse phase high performance liquid chromatographic method has been developed for the simultaneous estimation of N-acetyl cysteine (NAC) and cefexime from its fixed dose combination (FDC). The fixed dose combination of NAC and cefexime is used in the treatment of chronic obstructive pulmonary disease. Separation was achieved on Acclaim C18 (150 mm x 4mm.) with 25 mM potassium dihydrogen phosphate (pH 2.7) and acetonitrile in the ratio 90:10 v/v. The mobile phase was pumped at 1mL/min and quantification was carried out at 220 nm using a UV detector. The retention time of NAC and cefexime was 2.7min and 11.47 min respectively. The method was validated as per ICH Q2R1 guidelines. The method demonstrated linearity from10-90 µg/ml and accuracy was between 101.16-101.96%. The precision of the method was less than 2% in all the cases. The method was further applied in the assay of marketed formulation.