Quantitative Structure-Activity Relationship Analysis of the Anticancer Activity of Chloroethylnitrosourea Derivatives

Chloroethylnitrosoureas (CENUs) are important clinical antitumor agents. In the present work, the quantitative structure-activity relationship (QSAR) of CENUs is investigated by ab initio computations at MP2/6-311G(d,p) level of theory. The activation energies of the electrophilic center formation on the alpha- and the beta-carbon (E
_a

^alpha
and E
_a

^beta
), as well as the octanol- water partition coefficient (LogP), are selected as structural parameters. 37 kinds of CENUs with experimental anticancer therapeutic index (TI) are selected as models. Through numerical fitting for the computational data with the experimental anticancer TI, a computational formula is established to predict the anticancer activity of CENUs. The correct discrimination ratio by computations according to the experimental anticancer TI comes up to 94.6% through a five degrees classification.