DFT studies on the quantitative structure-activity relationship of N-(2-chloroethyl)-N′-cyclohexyl-N-nitrosoureas as anticancer agents

N-(2-chloroethyl)-N´-cyclohexyl-N-nitrosoureas (CCNUs) are widely applied as antitumor agents. However, researches have indicated that their decomposition products are inclined to cause secondary cancer. Hence it is necessary to probe into both carcinogenic and anticancer mechanism of such compounds so that effective anticancer drugs with lower toxicity can be obtained. In the present work, the DFT-B3LYP method with the basis set of 6-31+G(d, p) was employed to calculate the molecular geometries and electronic structures of 17 CCNUs. The charges of C₆ and (miLogP)² were selected as quantum chemical descriptors. The observed anticancer activity along with the two descriptors was used to establish the quantitative structure-activity relationship (QSARs). Through multiple linear regression analysis, a model was established as follows: log l/C = -0.042 × (miLogP)² + 11.783 × Q_C6 + 3.237. Here C refers to the molar concentration (mol/kg) of drugs producing a reduction of 1000-fold of leukemia cells to mice. This QSAR model can be applied to predict the anticancer activity of CCNUs, as well as elucidate their anticancer mechanism reasonably.