定量构效关系的原理、方法及其研究进展

介绍了定量构效关系(QSAR/QSPR)的原理、方法,综述了该领域的研究成果及其进展.重点论述了线性的启发式方法与径向基函数神经网络在定量构效关系研究中的应用,展望了该方法在各个学科的应用将会深入发展.     

蜂毒肽类似物的基因表达与构效关系研究

根据先前建立的蜂毒肽QSAR模型预测，为获得溶血活性相对最低，保留或提高抑菌活性的蜂毒肽类似物。设计了六条蜂毒肽类似物基因，采用P. pastoris表达系统，通过构建 pPICZα-A-Mel重组质粒，电击转化酵母。以α-factor为分泌信号，在GS115中分泌表达。以MDH、MMH筛选，诱导培养，6×His亲和层析纯化表达产物, Tricine-SDS-PAGE电泳证实。新设计的六条类似物基因表达后抑菌活性与天然序列蜂毒肽相比，四条增强，两条减弱。类似物【C】抑菌效价(U)为1.29，是重组天然序列蜂毒肽的1.6倍左右，活性最强，而重组天然序列蜂毒肽为0.7977。类似物【C】溶血活性比天然序列蜂毒肽降低至1/25。类似物【B】的表达量最高，为0.31mg/mL，其抑菌活性仅次于【C】。两种类似物的溶血活性降低至天然序列蜂毒肽的1/25左右，两种降低至1/20左右，还有两种降低至1/15左右。对蜂毒肽分子结构的优化设计合理，达到了保留或提高抑菌活性，降低溶血活性的目的。     

取代芳烃对剑尾鱼和稀有鮈鲫的生物活性模型

非氢原子的原子参数(gi)定义为:gi=(ni-1)0.5.mi.(tcti)αi-(-1)hi+ki(1+k2i)hβii.基于gi建构新的拓扑指数mL,并研究了含有Cl、OH、NO2、烷基等基团的取代芳烃急性毒性的定量构效关系(QSAR).这些化合物对剑尾鱼、稀有鲫的半数致死浓度(-lgLC50)与0阶指数(0L)的线性方程分别为:-lgLC50=-0.949 9+0.030 60L,-lgLC50′=-1.165 8+0.035 40L,它们的计算值与相应实验值颇为接近.     

Synthesis and insecticidal activities of new pyrethroid acid oxime ester derivatives

A series of compounds containing oxime-ester linkage in place of the ester linkage in pyrethroid ester are designed and prepared. Bioassay data of insecticidal activities of these compounds on Ostrinia nubilalis (H.) and Culex pipines (L.) are presented. Among them 4-dimethyaminobenzaldehyde oxime ester of 2,2,3,3-tetramethylcyclopropanecarboxylic acid and 4-dimethyamino benzaldehyde oxime ester of cyclopropanecarboxylic acid are found to be potent insecticide against Ostrinia nubilalis (H.). Structure-activity relationship of the compounds is discussed.     

Structure-activity relationship of endomorphins and their analogs

To study the structure-activity relationship of endomorphins (EMs), the action of opioid receptor binding (AORB), analgesic activity and vasodilator effects of EMs and their eight analogs were investigated, which were prepared by rationally replacing the 2-/3-amino acid (Aa) of EMs. The results showed: (ⅰ) The 2-Aa was comparatively more related to the selectivity of EMs while the 3-Aa to their affinity; (ⅱ) the analgesia and vasodilatation of EMs and their analogs were not completely dictated by their AORB (in vitro), the action of [D-Pro²]EM-2 was unusual; (ⅲ) EMs lost their analgesia in the central nervous system and their vasodilatation in the circulatory system with different mechanisms; the former was due to the degradation of some peptidase, and the latter possibly due to the feedback inhibition.     

对氨基苯甲酸酯类紫外吸收性能的定量构效关系——Ⅱ.化合物紫外吸收光谱的构效关系

对十个化合物的紫外吸收性能进行了测定。对其紫外吸收构效关系进行了探索,用振子强度f_n的概念来反映化合物的紫外吸收强度。结果表明f_n与PPP量子化学参数SOSC修之间存在着定量关系。在考虑到溶剂和不同取代基的影响后,发现紫外吸收频率和PPP量子化学参数——前线轨道能量差△E_(?),之间也有良好的线性关系。     

1-(2-羟基苄基)-2-苯基肼类衍生物的合成、表征及抑菌活性研究

依据邻羟基二苯醚类及肼类化合物的抗菌特性,以"邻羟苯基"为分子核心、-CH2NHNH-为桥基,构建了一类1-(2-羟基苄基)-2-苯基肼类衍生物.芳香胺为原料,经重氮化、还原、制得取代苯肼,与水杨醛缩合、NaBH4还原,合成了7种未见报道的化合物,抑菌测试表明,在质量分数为0.01%时,化合物对白色念珠菌的抑菌率高达100%具有强抑菌活性,对大肠杆菌抑菌率高于80.0%,对金黄色葡萄球菌有一定的抑菌活性.构效分析表明,苯环上取代基类型对化合物抑菌活性有重要影响,引入Br、Cl等卤原子,能显著增强化合物的抑菌活性,而引入NO2、CH3等强吸、供电基团,能显著降低其抑菌活性.     

二氨基吡啶[2,3-d]并嘧啶类化合物定量构效关系的研究

用Gaussion94程序的DFT／B3LYP方法,对抗癌活性类药物2,4-二氨基．5-甲基-6-(取代苯胺基)甲基吡啶[2,3-d]并嘧啶类化合物进行了量子化学计算．研究发现此类化合物结构与生物活性有直接关系,分子的HOMO轨道能级与分子活性有线性关系,说明此类化合物在发挥生物活性时以供电子为主．