QSAR of Clerodane Diterpenoids with Cytotoxic and Antitumoral Activity Against V-79 Cells

摘要

This work deals with diterpenoids of the clerodane type, compounds isolated from the extracts of different plant organs from trees mainly of the Flacourtiaceae family. The aim of the present work is to study Quantitative Structure-Activity Relationship (QSAR) on Casearins isolated from the crude plant extract of the leaves of the shrub tree Casearia sylvestris Swartz, Flacourtiaceae, that show cytotoxic activities against V-79 Chinese Hamster lung cells. In total, ca. 2080 descriptors and indices were calculated for the QSAR study using various softwares. The obtained QSARs with three descriptors were developed using two independent methods, Multiple Linear Regression (MLR) and Support Vector Machine (SVM), using a small set of molecules. For external validation of the MLR QSAR we employed a training/test set that was evaluated through criteria ruled by RQK fitness functions. Both MLR and SVM QSARs were validated using the same test set, where the SVM QSAR achieved the best results. Both QSARs were applied to a data set with 113 clerodane diterpenoids never tested before against the Chinese Hamster lung fibroblast V-79 cells, and also applied to thirteen new compounds which were build in silico, adding fluorine and chlorine atoms as substituents at specific positions of the clerodane diterpenoids. Encouraging results were obtained in both cases which serve as an indicator for further studies in silico and/or bioassay of these compounds as anticancer agents.