Application of MIA-QSAR in Designing New Protein P38 MAP Kinase Compounds Using a Genetic Algorithm

Multivariate image analysis quantitative structure-activity relationship (MIA-QSAR) study aims to obtain information from a descriptor set, which are image pixels of two-dimensional molecule structures. In the QSAR study of protein P38 mitogen-activated protein (MAP) kinase compounds, the genetic algorithm application for pixel selection and image processing is investigated. There is a quantitative relationship between the structure and the pIC50 based on the information obtained. (The pIC50 is the negative logarithm of the half-maximal inhibitory concentration ( IC50 ), so pIC50 = −log IC50 .) Protein P38 MAP kinase inhibitors are used in the treatment of malignant tumors. The development of a model to predict the pIC50 of these compounds was performed in this study. To accomplish this, the molecules were first plotted and fixed in the same coordinates in ChemSketch. Then, the images were processed in the MATLAB program. Partial least squares (PLS) model, orthogonal signal correction partial least squares (OSC-PLS) model, and genetic algorithm partial least squares (GA-PLS) model methods are used to generate quantitative models, and pIC50 prediction is performed. The GA-PLS model has the highest predictive power for a series of statistical parameters such as root mean square error of prediction (RMSEP) and relative standard errors of prediction (RSEP). Finally, the molecular junction (docking) was done for predicted molecules in quantitative structure activity relationship (QSAR) with an appropriate receptor and acceptable results were obtained. These results are good and proper for the prediction of compounds with better properties

Spectrophotometric Determination of the Dissociation Constants of Fluorescein in Micellar Media

The investigation of the dissociation equilibrium of fluorescein in aqueous micellar solution was determined spectrophotometrically at 25 °C and at ionic strength of 0.1 mol dm−3. For this purpose, the effect of nonionic (TX100), cationic (CTAB) and anionic (SDS) surfactants on the absorption spectra of fluorescein at different pH values were studied. To evaluate the pH-absorbance data, a resolution based on the combination of soft- and hard-modeling is applied. The acidity constants of all related equilibria are estimated using the whole spectral fitting of the collected data to an established factor analysis model. DATAN program was applied for determination of acidity constants. Results show that the pKa values of fluorescein are influenced as the percentages of an anionic and a cationic surfactant such as SDS and CTAB, respectively, are added to the solution of this reagent. Also, neutral surfactant such as TX100 only affects pKa1. Effects of surfactant on acidity constants and pure spectrum of each component are also discussed.</p