A density functional study of a new family of anticancer drugs: Paclitaxel, taxotere, epothilone, and discodermolide

We present a density-functional study of the paclitaxel, taxotere, baccatin III, epothilone-A, and discodermolide molecules in their gas phase. For each of these compounds we determine the geometry and the electronic structure of the ground state and of some isomers and analogues. We find that the central part of all these molecules is insensitive to changes in structure, orientation, and isomerization of its tail and is characterized by a rather large dipole that has similar orientation with respect to the molecular frame. These similarities extend also to the electronic structure. Our results provide an extended and consistent set of data to gauge classical force fields in view of the atomistic investigations of the interaction of these molecules with tubulin.