Volsurf Descriptors to Analyse Anti-HCV and Cytotoxic Activities of Sesquiterpene Lactones from Asteraceae Family

Mariane      Ballerini Fernandes; Michelle      Rossini; Ricardo      Stefani; Leoberto      Tavares; Vicente      de Paulo Emerenciano; Luciana      Scotti; Marcelo      Sobral da Silva; Marcus      Tullius Scotti

Abstract

Various significant anti-HCV and cytotoxic sesquiterpene lactones (SLs) have been characterized. In this work, the chemometric tool Principal Component Analysis (PCA) was applied to two sets of SLs and the variance of the biological activity was explored. The first principal component accounts for as much of the variability in the data as possible, and each succeeding component accounts for as much of the remaining variability as possible. The calculations were performed using VolSurf program. For anti-HCV activity, PC1 (First Principal Component) explained 30.3% and PC2 (Second Principal Component) explained 26.5% of matrix total variance, while for cytotoxic activity, PC1 explained 30.9% and PC2 explained 15.6% of the total variance. The formalism employed generated good exploratory and predictive results and we identified some structural features, for both sets, important to the suitable biological activity and pharmacokinetic profile.

Keywords: Anti-HCV, Cytotoxicity, GRID, Principal component analysis, Sesquiterpene lactones, VolSurf, Natural products, morphine, quinine, nucleophiles, HCV, WHO, cirrhosis, QSAR, methylene-lactone moiety, Multiple Linear Regression, Self-Organizing Maps, hydroxyl group, pharmacokinetic, ADME, 3D, GRID method, Parthenolide, Costunolide, Helenalin, Eudesmanolide, Germacronolide, carcinoma, AM1, SPARTAN, hydrophobicity, DRY, probes, PCA, PCs, OH2, Capacity factors descriptors, Integy moments descriptors, hydrophilic regions, RNA, hydrophobic, Fixed Elongation, biotransformation