3-D QSAR studies of microtubule stabilizing antimitotic agents towards six cancer cell lines

The antimitotic agent paclitaxel continues to play an important role in cancer chemotherapy. However, its inefficacy on certain resistant cells and toxic side effects had led to the search for new drugs with improved biological activity. Here the QSAR models for microtubule stabilizing anticancer agents were performed to correlate their physicochemical properties with biological activity. Single and multiple linear regression models for six cancer cell lines were obtained with R2 ≥ 0.65 and q2pre ≥ 0.6. Molecular mechanics energy and log P of the molecules account for the activity of taxanes towards B16 melanoma and breast cancer cells, respectively. The lowest unoccupied molecular orbitals and the number of nitrogen atoms in the structure account for the biological activity of epothilone derivatives and rest of the drugs towards ovarian cells. The relation between the structural properties of microtubule stabilizing antimitotic compounds and their activities on different cell lines are investigated in this paper. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.