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

• 来源期刊: 中国化学（英文版）
• 年，卷（期）: 2006,（11）
• 页码范围: 1531-1537
• 页数: 7页
• 语种: 英文

摘要

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.SomeQSARmodels 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 ClogP2. However, such descriptors can quite well describe a significant statistic quality and havearemarkable predictive activity according to the square of adjusted correlation coefficient ( RA2 =0.937) and the square of cross-validation coefficient (q2=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 pIC50 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 under standing the action mechanism and performing the molecular design or modification of this series of antimetastatic agents.