摘要
用量子化学密度泛函(DFT)及分子力学(MM+)方法,计算了一系列抗肿瘤喹唑啉衍生物分子的电子结构、几何结构及分子性质(广义结构参数),并通过回归分析,筛选出主要因素,建立定量构效关系(QSAR)方程。发现该类化合物分子的抗肿瘤活性与一些广义结构参数有密切关系,特别是苯环18位碳上取代基(R)的体积与表面积的比值r18,嘧啶环与苯环(C环)间的距离d,以及次低未占据分子轨道(NLUMO)的能量 NL与抗肿瘤活性显著相关,可通过取代基的选择与计算来筛选药效最佳的先导物。QSAR方程的拟合相关系数(R2)及交叉验证相关系数(q2)分别为0 8516和0 7146,表明所得模型具有可信的预报能力,可用以精确预测该系列化合物活性,并为设计抗肿瘤活性更高的喹唑啉衍生物及作用机理分析提供理论指导。
The computations of the electronic structures and some molecular properties of a series of quinazoline derivatives have been carried out by using the density functional theory (DFT) method of quantum chemistry and molecular mechanism method(MM+). Via a stepwise regression analysis, some main factors affecting the activity of the compounds were selected out, and the quantitative structure-activity relationship (QSAR) equation was established. It has been found that the antitumor activity of the quinazoline derivatives is predominantly related to some structural parameters. In particular, the ratio of the volumn with respect to the area of the substituent at site 18 on benzene ring, the distance between the C_7 and C_(16), as well as the energies of the next lowest unoccupied molecular orbitals (NLUMO) of the complexes are closely correlated with the antitumor activity. Since all factors in the QSAR equation are some computed electronic and geometric structural parameters, it will be very advantageous to selection of some precursors with excellent antitumor activity. The fitting relation coefficient R^2 and the cross-validation relation coefficient q^2 for the model established by this study are 0.851 6 and 0.714 6, respectively. The results suggest that this model has good predictability. The above results can offer some important theoretical guides in a design for novel quinazoline derivatives having higher antitumor activity and in an analysis of the action mechanism.
出处
《中山大学学报（自然科学版）》
CAS
CSCD
北大核心
2005年第2期49-52,共4页
Acta Scientiarum Naturalium Universitatis Sunyatseni
基金
广东省自然科学基金资助项目(021721)
关键词
喹唑啉
抗肿瘤活性
量子化学
密度泛函法
定量构效关系
quinazoline derivative
antitumor activity
quantum chemistry
DFT
the quantitative structure-activity relationship (QSAR)
