QSAR Studies on a Series of 7,8‐Dialkyl‐1,3‐diaminopyrrolo‐[3,2‐ f ]quinazolines with Anticancer Activity

The quantitative structure‐activity relationship (QSAR) studies on a series of 7,8‐dialkyl‐1,3‐diaminopyrrolo‐[3,2‐ f ]quinazolines, dihydrofolate reductase (DHFR) inhibitors as potential anticancer agents, have been carried out by using the density functional theory (DFT) method, molecular mechanics method (MM+) and statistical method. Some QSAR models based on their lipophilic and steric parameters were built up via a stepwise regression analysis. It is very interesting to find that the established optimal QSAR equation involves only two descriptors: lipophilicity indexes Clog P and Clog P 2 . However, such descriptors can quite well describe a significant statistic quality and have a remarkable predictive activity according to the square of adjusted correlation coefficient ( R 2 A =0.937) and the square of cross‐validation coefficient ( q 2 =0.911) of this equation. The results show that the lipophilicity is a main factor affecting the anticancer activity of this series of antimetastatic agents, and the obtained equation describes a parabolic correlation between pIC 50 and Clog P , and indicates a suitable range of Clog P (around 4.43) being very important for optimal pIC 50 values. These QSAR studies can offer some useful references for understanding the action mechanism and performing the molecular design or modification of this series of antimetastatic agents.