6-异位-5,8-O-二甲基乙酰紫草素衍生物的2D/3D-QSAR研究  

2D/3D-QSAR studies of 6-isomers of 5,8-O-dimethyl acylshikonin derivatives

作　　者：李国栋[1] 彭发[1] 陈兰美[1] 陈锦灿[1] 郑康成[2] 

机构地区：[1]广东医学院药学院,广东湛江524023 [2]中山大学化学与化学工程学院,广东广州510275

出　　处：《化学研究与应用》2015年第2期113-121,共9页Chemical Research and Application

基　　金：广东省自然科学基金(9452402301001941)资助;广东省医学科研基金(B2013297;A2014473)资助

摘　　要：本文综合运用密度泛函理论(DFT)、分子力学(MM2)和统计学等方法对22个具有抗人体乳腺癌(MDA-MB-231)活性的6-异位-5,8-O-二甲基乙酰紫草素类衍生物进行二维(2D)定量构效关系(QSAR)研究,同时运用比较分子相似性指数分析(Co MSIA)方法进行三维(3D)QSAR研究。所建最优2D-QSAR方程的留一法交叉验证系数(q2)和拟合相关系数(R2)分别为0.833和0.900;Co MSIA(SEHA)模型的q2和非交叉验证系数(r2)分别为0.624和0.999,预测相关系数R2pred为0.838,表明所建立的2D/3D-QSAR模型都具有良好的统计学意义及合理、可信的预报能力,可以预测未知化合物的活性。研究结果为理解该类化合物的作用机理和设计合成更高活性的新化合物提供理论参考。A theoretical study on the two-dimensional（ 2D） and three-dimensional（ 3D） quantitative structure-activity relationships（ QSAR） of 22 novel compounds of 6-isomers of 5,8-O-dimethyl acylshikonin derivatives against the breast cancer cell line（ MDAMB-231） has been carried out. A combined method of the Density Functional Theory（ DFT）,Molecular Mechanics（ MM2） and statistics as well as the comparative molecular similarity indices analysis（ Co MSIA） was applied to develop 2D and 3D-QSAR models. To the final optimal 2D-QSAR model,the leave-one-out cross-validated value（ q2） was 0. 833,the square of correlation coefficient（ R2） was 0. 900. And for the optimal Co MSIA（ SEHA） model,the corresponding q2 and the non-cross-validated value（ r2）were 0. 624 and 0. 999,respectively. The final 2D /3D-QSAR models show good statistical quality and satisfactory predictive ability,and could be used to predict activities for unknown molecule. The results and discussion can provide theoretical guidances for understanding the action mechanism and further designing new antitumor drugs.

关 键 词：紫草素衍生物 5 8-O-二甲基-1 4-萘醌 抗肿瘤活性 定量构效关系 比较分子相似性指数分析法 

分 类 号：O641[理学—物理化学]