Predictive Modeling of Phenylpiperazine Derivatives for Renin Inhibition: QSAR Study of Phenylpiperazine Derivatives as Renin Inhibitors

The renin–angiotensin–aldosterone system is the well-established endocrine system having significant role in preserving hemodynamic stability. Renin is secreted from the juxtaglomerular cells of the kidney. Phenylpiperazine derivatives have been reported as human renin inhibitor. To do the study, a predictive QSAR modeling for 27 phenylpiperazine derivatives as renin enzyme inhibitors was used. The IC50 values for purified human renin were taken as biological activity. Physicochemical properties were calculated on Dragon software, version 5.5. Hierarchical Multiple Regression was performed to obtain quantitative structure-activity relationship model which again validated internally and externally. The selected best QSAR model had the correlation coefficient (R2) of 0.843, and predicted correlation coefficient (R2pred) of 0.867. The predictive ability of the selected model was established by leaving one-out cross-validation. Different Rm2 matrices were also calculated to validate the model externally. The quantitative structure activity relationship study indicates that CIC2, BIC2, and R7v descriptors have a very important role in renin enzyme and ligand interaction. The developed model can be applied to design new effective renin enzyme inhibitors

Application of Chemometrics in Simultaneous Spectrophotometric Quantification of Etophylline and Theophylline: The Drugs with Same Chromophore: Chemometrics in Simultaneous Spectrophotometric Determination

Chemometric techniques in spectral analysis have gained importance in the quality control of the drugs mixtures and pharmaceutical formulations containing two or more drugs with overlapping spectra. Since theophylline and etophylline have common chromophore, they cannot be analyzed simultaneously using conventional UV methods. Simultaneous spectrophotometric determination of etophylline and theophylline was performed by partial least-squares (PLS) and principal component regression (PCR) methods. The absorbance values in the UV-Vis spectra were measured for the 71 wavelength points (from 230-300) in the spectral region 200-400 nm considering the intervals of 1 nm. The accuracy and the precision of the methods were determined and validated by analyzing synthetic mixtures of the drugs. The numerical calculations were performed with the ‘Unscrambler 10.3 X software. The calibration ranges were found to be 6-30 μg/ml for etophylline and 2-10 μg/ml for theophylline. The chemometrics analysis methods were satisfactorily applied to the simultaneous determination of etophylline and theophylline in the tablet dosage form

Docking, synthesis and biological evaluation of pyridine ring containing Diaryl urea derivatives as anticancer agents

A novel series of pyridine ring containing diaryl urea derivatives (R1-R9) were synthesized in four chemical steps using pyridine-2-carboxylic acid as starting material. The synthesized compounds were design by using Autodock vina in the crystal structure of the Kinase domain of Human B-raf (PDB ID: 4DBN) to get insights into structural requirements for anticancer activity. In vitro anticancer activity against cell line (MCF-7) showed that compounds R3, R6 and R9 were found to be the most potent (Docking score: > -12, IC50 = 17.39 µM) among the synthesized molecules