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摘要:在药物领域迅速发展的今日，恶性肿瘤依然肆虐着人类的生命，严重影响着人类的健康生活，令众多学者也头疼不已，成为世界上最难攻克的难关之一。姜黄素是从姜科等科目的一些植物的根茎中提取而出的有效活性成分，对其进行结构的改造，使其能够具有强效的抗肿瘤活性。本文使用计算机辅助药物设计（CADD）的SYBYL-X 2.0设计软件，根据32个姜黄素类似物具有对传代性的人肺腺癌细胞A549的GI50（半生长抑制浓度）值，进行3D-QSAR研究，建立有效且预测能力较好的CoMFA、CoMISA模型，通过建立GALAHAD药效团模型对ZINC库进行虚拟筛选。CoMFA模型的交叉验证系数q2=0.570，相关系数R2=0.968，标准偏差为0.094，F值为146.809；CoMISA模型的交叉验证系数q2 =0.671，最佳主成分数为5，相关系数R2=0.937，标准偏差为0.119，F值为124.733，并验证了CoMFA、CoMISA模型具有较好的统计学意义与预测能力，通过分析CoMFA与CoMISA色块图设计姜黄素类似物新分子，并通过模型对实验室合成类似物与新分子进行对人肺腺癌细胞A549的GI50（半生长抑制浓度）值的预测。57189
毕业论文关键词: 姜黄素；SYBYL-X 2.0；3D-QSAR；A549；药效团；虚拟筛选
Design of Novel cucurmin analogues as antitumors based on 3D-QSAR
Abstract: The rapid development in the field of medicine today, malignant tumors still raging human life, a serious impact on the health of human life, so many scholars have a headache, become one of the world most difficult to overcome the difficulties. Curcumin is an active ingredient extracted from the roots of some plants of the family and other subjects, and the structure of them is transformed, so that it can have a strong anti tumor activity. In this paper, the use of computer aided drug design (CADD) SYBYL-X 2.0 design software, according to the 32 curcumin analogues with passage of human adenocarcinoma of lung cancer cell line A549 GI50 (half inhibitory concentration) values, 3D-QSAR study, to establish an effective and predictive ability good CoMFA, CoMISA model, through the establishment of Galahad pharmacophore model for virtual screening of zinc base. The CoMFA model cross validation coefficient q2 =0.570, correlation coefficient R2=0.968 and the standard deviation was 0.094, F=146.809; CoMISA model of cross validation coefficient q2 =0.671, best main fraction 5, the correlation coefficient R2=0.937, standard deviation is 0.119, F =124.733, and validate the predictive CoMFA and CoMISA model has good statistical significance and predictive ability. Through analysis CoMFA and CoMISA color chart design of curcumin analogues molecules, and through the model of synthetic analogues of laboratory and new molecular were on human lung adenocarcinoma cell line A549 GI50 (half inhibitory concentration) values.
Keywords: cucurmin；SYBYL-X 2.0；3D-QSAR；A549；pharmacophore；virtual screening
目录
1 前言 1
1.1 研究背景与目的 1
1.2 研究现状与进展 1
1.3 研究意义与内容 4
2 计算方法与理论 5
2.1 计算机辅助药物设计 5
2.2 三维定量构效关系（3D-QSAR) 5
2.3 SYBYL-X2.0软件简介 6
2.4 研究方法概述 6
2.4.1 分子结构搭建与优化 6
2.4.2 分子力场选择 7
2.4.3 分子叠合 7
2.4.4 建立CoMFA和CoMSIA模型 7
2.4.5 预测活性值与设计新分子
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