Breast cancer is the second leading cause of
cancer death among women in the United States. Two
taxane analogues,
taxol and
taxotere, are the most important
antimitotic drugs currently in clinical use for the treatment of breast
cancers. However, recent reports have indicated that the use of these drugs often results in various undesired side effects as well as multi-drug resistance. These limitations have led to the development of new
taxane derivatives with fewer side effects, superior pharmacological properties, and improved anticancer activity to maximize the induced benefits for
breast cancer patients. Herein, four series of
taxane derivatives were used to correlate their inhibitory activities against
breast cancer cells with their hydrophobic and steric properties in order to understand their chemical-
biological interactions. The resulting QSARs show that the inhibitory activities of
taxane analogues against breast
cancers are mainly dependent either on their hydrophobicity or the hydrophobic/molar refractivity descriptor of their substituents. A parabolic correlation with MR(Y) is the most encouraging example, in which the optimum value of this parameter is well defined. We believe this correlation may prove to be an adequate predictive model that can help provide guidance in design and synthesis and subsequently yield highly specific compounds that may have high anti-
breast-cancer activity with fewer side effects and superior pharmacological properties. On the basis of this QSAR model, five compounds are suggested as potential synthetic targets. Internal (cross-validation (LOO-q(2) and LMO-q(2)), quality factor (Q), Fischer statistics (F), and Y-randomization) and external validation tests have validated all the QSAR models.