College of Chemistry, Sichuan University, Chengdu, 610064, China.
Interdiscip Sci. 2011 Jun;3(2):121-7. doi: 10.1007/s12539-011-0077-6. Epub 2011 May 4.
A quantitative structure-activity relationship (QSAR) of a series of tanshinone compounds with cytotoxicity against murine leukemia cell lines P-388 has been studied using density functional theory (DFT) method combined with statistical analysis. Four main independent factors contributing to the cytotoxicity including the maximum molecular electrostatic potential at the SAS surface (SAS (max)), the average nucleophilic superdelocalizability (ANS), the dihedral between ring A and B (u) and the net atomic charge of C (12) (Q(C (12))) were selected by stepwise multiple regression method, then the QSAR equation was established via multiple linear regression (MLR) analysis. These descriptors accounted for 74.2% of the variation in the in vitro biological activity among the tanshinone analogues. The QSAR equation was used to estimate the cytotoxicity for new compounds of this series by calculating the four descriptors. Based on this model, six new compounds with higher cytotoxicity were theoretically designed.
应用密度泛函理论（DFT）方法结合统计学分析，研究了一系列丹参酮化合物对 P-388 白血病细胞系的细胞毒性的定量构效关系（QSAR）。通过逐步多元回归法，选择了对细胞毒性有贡献的四个主要独立因素，包括 SAS 表面的最大分子静电势（SAS（max））、平均亲核超离域性（ANS）、环 A 和 B 之间的二面角（u）以及 C（12）的净原子电荷（Q（C（12））），然后通过多元线性回归（MLR）分析建立了 QSAR 方程。这些描述符解释了丹参酮类似物之间体外生物活性变化的 74.2%。通过计算这四个描述符，QSAR 方程被用来估计该系列新化合物的细胞毒性。基于该模型，理论上设计了六个具有更高细胞毒性的新化合物。
