Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC~ 8 μM) was the most potent among all 60 compounds, whose potency is comparable with broad spectrum antibiotics like ciprofloxacin and streptomycin and three times more potent than pyrazinamide. Additionally, compound 40 was also less selective and hence non-toxic towards the human live cell lines-LO2 in its MTT assay. Compounds 30, 27, 50, 41, 51, and 60 have exhibited streptomycin like activity (MIC~16–18 μM). Fluorinated chalcones, pyridine and pyran derivatives were found to occupy prime position in thymidylate kinase enzymatic pockets in molecular docking studies. The molecule 40 being most potent had shown a binding energy of -9.67 Kcal/mol, while docking against thymidylate kinase, which was compared with its in vitro MIC value (~8 μM). These findings suggest that 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs

Simultaneous Quantification of Paracetamol and Meloxicam in Tablets by High Performance Liquid Chromatography

Purpose: To develop and validate a simple, rapid and inexpensive RP-HPLC method for the simultaneous estimation of paracetamol and meloxicam in tablets. Methods: For the analysis of the drugs, chromatographic analysis was performed on XTerra symmetry C18 column (100 × 4.6 mm, 5 μ particle size) with mobile phase consisting of methanol and phosphate buffer (pH 9.2) in the ratio of 50:50 v/v, at a flow rate of 0.8 mL/min and eluents monitored at 244 nm. The method was validated for linearity, accuracy, precision, robustness and application for assay as per International Conference on Harmonization (ICH) guidelines. Results: The retention times of paracetamol and meloxicam were 2.467 and 4.971 min, respectively. The calibration curves of peak area versus concentration, which was linear from 5 - 60 μg/mL for paracetamol and 1 - 12 μg/mL for meloxicam, had regression coefficient (r2) greater than 0.999. The method had the requisite accuracy, precision, and robustness for simultaneous determination of paracetamol and meloxicam in tablets. Conclusion: The proposed method is simple, low-cost, accurate, precise and can be successfully employed in routine quality control for the simultaneous analysis of paracetamol and meloxicam in tablets