Taxane analogues against lung cancer: a quantitative structure-activity relationship study.

Lung cancer is the second most common cancer in both men (after prostate cancer) and women (after breast cancer). The microtubule-stabilizing taxane such as docetaxel is the only agent currently approved for both first- and second-line treatment of advanced non-small cell lung cancer. Although docetaxel has made significant progress in the treatment of lung cancers either using alone or in combination with various novel targeted agents, its use often results in various undesired side-effects. These limitations have led to the search for new taxane derivatives with fewer side-effects, superior pharmacological properties, and improved anticancer activity to maximize the induced benefits for lung cancer patients. Herein, four series of taxane derivatives were used to correlate their inhibitory activities against lung cancer cells with hydrophobic and steric descriptors to gain a better understanding of their chemical-biological interactions. A parabolic correlation with MR(Y) is the most encouraging example, in which the optimum value of this parameter is well defined. On the basis of this quantitative structure-activity relationship model, six compounds (3-23 to 3-28) are suggested as potential synthetic targets. Internal (cross-validation (q(2)), quality factor (Q), Fischer statistics (F ) and Y-randomization) and external validation tests have validated all the quantitative structure-activity relationship models.