Objective To establish an efficient 2D-QSAR model for Novobiocin analogues to predict their inhibitory activities on pancreatic cancer cell (PL45) and expect that the theoretical results can offer some useful references for understanding the inhibition mechanism and directing the design and synthesis of more potential an-ti-PL45 agents. Methods The Two-dimensional Quantitative Structure-activity Relationship (2D-QSAR) of 23 Novobiocin analogues, which exhibited inhibitory activities of PL45, had been studied with a combined method of density functional theory ( DFT) , molecular mechanics ( MM+) and statistics. Result The established 2D-QSAR model showed a reasonable regressive performance (R = 0.767). Conclusion The charge on oxygen atom of Novobiocin molecules, QO1, plays a decisive role in determining the inhibitory activity of PL45, and the molecular surface of flavonoids, SR, plays an important role in determining the inhibitory activity as well.%目的 为Novobiocin类化合物建立一个有效的2D-QSAR模型来预测其抑制胰腺癌细胞(PL45)的活性,对抑制胰腺癌细胞(PL45)机理研究和发现高活性的Novobiocin类化合物提供参考和帮助.方法 采用密度泛函理论、分子力学和统计学相组合的方法,对23个具有抑制胰腺癌细胞(PL45)的Novobiocin类化合物进行了二维的定量构效关系(2D-QSAR)的研究.结果 所建立的2D-QSAR方程具有较好的回归性(R达到0.767).结论 Novobiocin类化合物分子的酰胺键的氧原子荷电量(QO1)对PL45的抑制活性起着关键的作用；同时,Novobiocin类化合物分子的R基团的大小,SR,也对PL45的抑制活性起着重要的作用.
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