QSAR Study Of Anti-Prion Activity Of 2-Aminothiazoles
2-aminothiazoles is a class of compounds capable of treating life-threatening prion diseases. QSAR studies on a set of forty-seven 2-aminothiazole derivatives possessing anti-prion activi- ty were performed using multivariate analysis, which comprised of multiple linear regression (MLR), artificial neural network (ANN) and support vector machine (SVM). The results indi- cated that MLR afforded reasonable performance with a correlation coefficient (r) and root mean squared error (RMSE) of 0.9073 and 0.2977, respectively, as obtained from leave-one- out cross-validation (LOO-CV). More sophisticated learning methods such as SVM provided models with the highest accuracy with r and RMSE of 0.9471 and 0.2264, respectively, while ANN gave reasonable performance with r and RMSE of 0.9023 and 0.3043, respectively, as obtained LOO-CV calculations. Descriptor analysis from the regression coefficients of the MLR model suggested that compounds should be asymmetrical molecule with low propensity to form hydrogen bonds and high frequency of N content at topological distance 02 in order to provide good activities. Insights from QSAR studies is anticipated to be useful in the design of novel derivatives based on the 2-aminothiazole scaffold as potent therapeutic agents against prion diseases.