Synthesis and pharmacological evaluation of novel 1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one derivatives as potential antimicrobial agents

Novel compounds of biological interest were synthesized by in situ reduction of Schiff’s base of 5,6-dimethoxy indanone and 1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one in the presence of Ti(OiPr)₄ and NaBH₃CN. Further alkylation using different alkyl/aryl halides in the presence of NaH in DMF gave a series of novel compounds. A formation of newly synthesized compounds was confirmed on the basis of their spectral and elemental analysis. Further these compounds were screened for their antimicrobial activity and found to have promising antibacterial and antifungal activity.     

Repeat Analysis and Incurred Sample Reanalysis: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

The A7 harmonization team (A7 HT), a part of the Global Bioanalysis Consortium (GBC), focused on reviewing best practices for repeat analysis and incurred sample reanalysis (ISR) as applied during regulated bioanalysis. With international representation from Europe, Latin America, North America, and the Asia Pacific region, the team first collated common practices and guidance recommendations and assessed their suitability from both a scientific and logistical perspective. Subsequently, team members developed best practice recommendations and refined them through discussions and presentations with industry experts at scientific meetings. This review summarizes the team findings and best practice recommendations. The few topics where no consensus could be reached are also discussed. The A7 HT recommendations, together with those from the other GBC teams, provide the basis for future international harmonization of regulated bioanalytical practices.     

Development and Validation of a Liquid Chromatographic Method for Estimation of Dicyclomine Hydrochloride,Mefenamic Acid and Paracetamol in Tablets

Liquid chromatographic method was developed for simultaneous quantitative determination of dicyclomine hydrochloride, mefenamic acid and paracetamol in their combined dosage form. The separation was achieved using a C₁₈ column (250×4.6 mm id, 5 μm) using acetonitrile:20 mM potassium dihydrogen phosphate 70:30 (v/v) adjusted to pH 4 using orthophosphoric acid as mobile phase at a flow rate of 1 ml/min and detection at 220 nm. Separation was completed within 12 min. The retention times of dicyclomine hydrochloride, mefenamic acid and paracetamol were 3.8, 9.3 and 2.5 minutes respectively. The proposed method was found to have linearity in concentration range of 10–100 μg/ml for dicyclomine hydrochloride, 0.05-10 μg/ml for mefenamic acid and 0.1−20 μg/ml for paracetamol. The developed method has been statistically validated and was found to be simple, precise, reproducible and accurate. The developed and validated method was successfully used for the quantitative analysis of commercially available dosage form.     

Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (6g) on chronic unpredictable mild stress-induced changes in behavioural and brain oxidative stress parameters in mice

Aim:

The aim of the study was to evaluate a novel 5 HT₃ receptor antagonist (6g) on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body''s reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to human depression, and such animal models can be used for the preclinical evaluation of antidepressants.

Materials and Methods:

In the present study, a novel and potential 5-HT₃ receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) with good Log P (3.08) value and pA₂(7.5) values, synthesized in our laboratory was investigated to study the effects on chronic unpredictable mild stress (CUMS)-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour.

Results:

The results showed that CUMS caused depression-like behaviour in mice, as indicated by the significant (P < 0.05) decrease in sucrose consumption and locomotor activity and increase in immobility the forced swim test. In addition, it was found that lipid peroxidation and nitrite levels were significantly (P < 0.05) increased, whereas glutathione levels, superoxide dismutase and catalase activities decreased in brain tissue of CUMS-treated mice. ‘6g’ (1 and 2 mg/kg, p.o., 21 days) and fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly (P < 0.05) reversed the CUMS-induced behavioural (increased immobility period, reduced sucrose preference and decreased locomotor activity) and biochemical (increased lipid peroxidation; decreased glutathione levels, superoxide dismutase and catalase activities). However fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly decreased the nitrite level in the brain while ‘6g’ (1 and 2 mg/kg, p.o., 21 days) did not show significant (P < 0.05) effect on the nitrite levels in brain.

Conclusion:

Compound ‘6g’ exerted antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant mechanisms.KEY WORDS: 5-HT₃ receptor antagonist, chronic unpredictable mild stress, depression, oxidative stress     

The Relationship of Visiting Insect Diversity and Density of Valeriana jatamansi with Increasing Altitude in Western Himalaya

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - In light of the recent evidences that pollinators have a significant implication for maintenance of...     

Total Phenolics,Tannins and Antioxidant Activity in Twenty Different Apple Cultivars Growing in West Himalaya,India

The present study evaluated phenolics and antioxidant activities in fully ripened fruits of 20 different apple cultivars e.g., Royal Delicious, Fanny, Gale Gala, Esopus Spitzenburg, King David, Winter Banana, Buckinghum, Super Chief, Breven, Red Fuji, Organ Spur, Tompking County, Red Gold, Golden Spur, Vance Delicious, Red Delicious, Macintosh, Rymer, Bhura Delicious, and Richa Red growing at different locations/elevations of Uttarakhand, West Himalaya, India. Total phenolics and tannins varied significantly among cultivars and the maximum content was recorded in Bhura Delicious (phenolics—3.77 mg GAE/g fw; tannins—16.47 mg TAE/g fw) as compared to others. Antioxidant activity using different in vitro assays showed highest activity in Bhura Delicious and lowest in Esopus Spitzenburg. A significant (p < 0.001) positive relationship was found between total phenolics and ABTS (r = 0.816), FRAP (r = 0.797) and DPPH (r = 0.862) assays. Phenolics and antioxidant activity exhibited significantly (p < 0.05) higher content in the peel as compared to whole fruit and flesh portion. Based on the results, it is concluded that Bhura Delicious is one of the promising sources of phenolics and antioxidant activity and, therefore, recommended for large scale plantation to harness its potential.

     

Aspirin dose and six-month outcome after an acute coronary syndrome

OBJECTIVES: This study was designed to compare the efficacy of low and intermediate aspirin doses in acute coronary syndromes. BACKGROUND: Little is known of the comparative efficacy of low and intermediate aspirin doses in this setting. METHODS: We compared six-month death, myocardial infarction (MI), and stroke in patients with unstable angina or acute MI discharged while receiving low (<150 mg) or intermediate (> or =150 mg) aspirin therapy in the GUSTO IIb and PURSUIT trials (n = 20,521). We used multivariable analysis and performed a propensity analysis in order to adjust for baseline imbalances between the groups. RESULTS: Aspirin doses <150 mg were prescribed to 29.9% (6,128) of patients. By six months, 6.4% of the patients (1,310 of 20,521) had a primary event, 6.2% of the patients receiving <150 mg and 6.6% of the patients receiving aspirin doses > or =150 mg (hazard ratio [HR] 1.06 [95% confidence interval (CI) 0.94 to 1.19], p = 0.35). After adjusting for baseline imbalances and the propensity score for discharge aspirin dose, there was no effect of aspirin dose on the composite end point at six months (HR 0.92 [95% CI 0.79 to 1.07], p = 0.28). However, the higher aspirin dose was associated with a reduction in six-month MI (HR 0.79 [95% CI 0.64 to 0.98], p = 0.03). The outcome was similar when patients were matched on the basis of the propensity score for aspirin dose (HR for death/MI/stroke 0.94 [95% CI 0.80 to 1.12], p = 0.51), although stroke occurred significantly more frequently among patients receiving the higher aspirin dose (HR 1.74 [95% CI 1.01 to 3.02] p = 0.05) and the effect on MI was no longer apparent. CONCLUSIONS: Although these data are non-randomized, they suggest that the aspirin dose upon discharge may influence the clinical course after unstable angina or acute MI.