对氨基苯甲酸酯同系物形成细胞色素P450代谢中间体络合物的定…

细胞色素Ｐ４５０（Ｐ４５０,Ｅｃ,１．１４．１４．１）是一种十分重要的催化氧化反应的酶,本文测定了１２个对氨基苯甲酸酯用系物与Ｐ４５０相互作用而形成Ｐ４５０代谢中间体络合物的活性,用半经验分子轨道法ＭＮＤＯ－ＰＭ３计算得到了这些同系物的分子轨道指数,并用逐步多元回归分析法导出了活性与分子轨道指数及正辛醇／水分配系数的对数值之间的定量结构与活性关系。结果表明,对苯氨基苯甲酸脂同系物形成Ｐ４５０代谢中     

对氨基二苯醚类化合物与细胞色素P450相互作用的定量与活性关系

对氨基二苯醚类化合物是结构色素Ｐ４５０（Ｐ４５０）的一种准不可逆抑制剂。本文测定了１７种这类化合物生成Ｐ４５０代谢中间体络合物的活性和抑制Ｐ４５０催化氧化氨基比林脱甲基的活性。用逐步多元回归分析法导出了这两种活性与Ｈａｎｓｃｈ理化参数或分子轨道指数之间的定量结构与活性关系（ＱＳＡＲ）。结果表明：这两种活性都与取代基的脂溶性参数之（Σπ）和间位的立体性参数Ｅｓ（３′）等Ｈａｎｓｃｈ理化参数或最低未占据分子轨道级（ＥＬＵＭＯ）和原子净电荷的绝对值之和（ΣＱ）等分子轨道指数相关;生成Ｐ４５０代谢中间体络合物的活性还与取代基的电性参数之和（Σσ）和邻位和立体性参数（Ｅｓ（２′）相关。两种活性之间存在很好的相关性。     

用Hückel分子轨道法研究苯并吖啶类衍生物的致癌活性与电子结构的相关性

本文对苯并[a]吖啶和苯并[c]吖啶衍生物中具有较确切致癌活性标度的40个化合物,进行了HMO计算。对计算所得的分子轨道参数进行了多元回归分析,建立了致癌活性与分子轨道参数的定量关系式。该式对致癌与非致癌物质的正确区分率为90％。     

对氨基二苯醚类化合物与细胞色素P450相互作用的定量与活性关系

对氨基二苯醚类化合物是结构色素Ｐ４５０（Ｐ４５０）的一种准不可逆抑制剂。本文测定了１７种这类化合物生成Ｐ４５０代谢中间体络合物的活性和抑制Ｐ４５０催化氧化氨基比林脱甲基的活性。用逐步多元回归分析法导出了这两种活性与Ｈａｎｓｃｈ理化参数或分子轨道指数之间的定量结构与活性关系（ＱＳＡＲ）。结果表明：这两种活性都与取代基的脂溶性参数之和（Σπ）和间位的立体性参数Ｅｓ（３＇）等Ｈａｎｓｃｈ理化参数或最低未     

对氨基苯甲酸酯同系物形成细胞色素P_（450）代谢中间体络合物的定量结构与活性关系

细胞色素Ｐ４５０（Ｐ４５０,Ｅｃ１．１４．１４．１）是一种十分重要的催化氧化反应的酶。本文测定了１２个对氨基苯甲酸酯同系物与Ｐ４５０相互作用而形成Ｐ４５０代谢中间体络合物的活性,用半经验分子轨道法ＭＮＤＯ－ＰＭ３计算得到了这些同系物的分子轨道指数,并用逐步多元回归分析法导出了活性与分子轨道指数及正辛醇／水分配系数的对数值（ＬｏｇＰ）之间的定量结构与活性关系（ＱＳＡＲ）。结果表明：对氨基苯甲酸脂同系物形成Ｐ４５０代谢中间体络合物的活性与原子净电荷的绝对值之和（∑Ｑ）和ＬｏｇＰ均具有很好的抛物线型相务性,同时,ＬｏｇＰ与∑Ｑ之间也存在相当好的相关性。     

环保好伙伴——刚毛藻

水污染问题是世界各国高度重视的环境问题,减少废水排放量、治理污水已列入城建的重点.以我国的重工业省份山西省为例,煤焦废水、工业废水的污染尤为严重,所含污染物主要有苯系物、氟化物、氯苯类化合物和酚类化合物等.苯系物是环境中毒性较大的污染物,多存在于焦化、造纸、橡胶和家装材料等工业废水中.     

三种工业废水对大型Zao毒性的研究

利用大型蚤（Daphnia magna Straus)对造纸、印染、化工等三种有机污染废水进行毒性试验,并对三种废水中的有机污染物进行色－质联机定性分析。在造纸、印染、化工废水中分别检出有机污染物32、49和36种,其中具有“三致”作用的分别占8、14和14种,试验结果表明,三种工业废水在有机污染程度（CODcr）相同的情况下,毒性大小主要和废水中“三致”物的种类和数量有关。三种废水对大型蚤24hLC50值分别为：造纸27．54％（23．23％－32．66％）,印染8．31％（6．92％－10．00％）,化工4．47％（3．56％－5．60％）;剂量－反应回归方程分别为造纸Y＝4．17x-1.0,印染Y＝3．77x＋1．53,化工Y＝3．64x＋2．63。     

人胎肝中两种抑制肿瘤细胞生长活性成分的分离鉴定及功能研究

胎儿组织中存在低分子肿瘤抑制物。胎肝细胞的甲醇－丙酮提取物中保留有大部分抑瘤活性。用体外液体培养条件下对人急性粒系白血病细胞系（ＨＬ－６０）的抑制作用为指标,跟踪分离过程。提取物经反相Ｃ１８中压液相色谱、Ｓｅｐｈａｄｅｘ ＬＨ－２０凝胶色谱及正相高效液相色谱分离得到两种活性物质,经ＮＭＲ和ＨＲＭＳ鉴定为７－酮基胆固醇（７－ｋｅｔｏｃｈｏｌｅｓｔｅｒｏｌ,７－ＫＣ）和７－β－羟基胆固醇（７－β－ｈｙ     

有机化合物结构与活性定量关系在水生毒理学上的应用

本文阐述了有机化合物结构与活性定量（QSAR）在水生毒理学上的应用,在我国应开展以下工作;水生毒理学家建立一套适合于QSAR建模要求的毒性试验体系;环境化学家寻找最佳结构参数,由此建立起相关性较好的QSAR模型,预测毒物的毒性和中毒机理。     

灰黑拟牛肝菌的化学成分

从担子菌灰黑拟牛肝菌（Boletopsis grisea)新鲜子实体的乙醇提取物中首次分离得到10个化合物,包括8个酚性成分,1个含硫成分和1个脑苷脂,它们的结构经各种波谱数据分别鉴定为3－（4－乙酰氧基苯）－1,2,4,7,8－五乙酰氧基二苯并呋喃（1）,3－（4－乙酰氧基苯）－1,2,4－三乙酰氧基－7,8－二羟基二苯并呋喃（2）,3－（4－羟基苯）－1,2－二乙酰氧基－4,7,8－三羟基二苯并呋喃（3）,2,3－二乙酰氧基－4′,4″,5,6－四羟基对联三苯（4）,对苯二酚（5）,对羟基苯甲酸（6）,茴香酸（7）,对羟基苯甲醛（8）,硫代乙酐（9）和1－O－吡喃葡萄糖基－（2S,3R,4E,8E,2′R）-2-N-(2′-羟基棕榈酰）－9－甲基－4,8－sphin-gadienine(10)。其中化合物1,2,3有报道对5－脂氧化酶具有选择性抑制活性。4,9,10均为首次从该属真菌中分离得到。     

Quantitative structure-activity relationship analysis of phenolic antioxidants

In this report, the quantitative structure-activity relationship (QSAR) analyses of substituted phenols, vitamin E derivatives and flavonoids are presented. Two models have been derived using calculated parameters such as the heat of formation (H_f), the energy of the lowest unoccupied molecular orbital of radicals (E_lumo-r), the energy of the highest occupied molecular orbital of the parent compounds (E_homo) and the number of hydroxyl groups (OH). These models can be used to estimate the redox potentials or antioxidant activities of new substituted phenolic compounds or vitamin E derivatives. The Trolox equivalent antioxidant capacities (TEACs) of 42 different flavonoids are found to be mainly governed by the number and location of hydroxyl groups on the flavonoid ring system.     

肼基单胺氧化酶抑制剂活性与电子结构构效关系的计算分析

采用量子化学方法,在DFT/B3LYP/6-31G*基组水平上对肼基单胺氧化酶抑制剂进行了几何构型优化和电子结构计算.根据计算结果,分析了肼基单胺氧化酶抑制剂的抑制活性与电子结构的构效关系,结果表明,肼基单胺氧化酶抑制剂衍生物的活性与最低空轨道的能量E_LUMO与最高占据轨道的能量E_HOMO的差值、分子偶极矩和苯环上5位碳原子电荷密度有显著相关性.     

QSAR studies on antimalarial 2,4-diamino-6-quinazoline sulfonamides

The present paper discusses QSAR studies on antimalarial 2,4-diamino-6-quinazoline sulfonamide derivatives using electronic parameters, namely energy of highest occupied molecular orbitals (EH), energy of lowest unoccupied molecular orbitals (EL) and charge density (CD). The results have shown that better results are obtained by introducing dummy parameters (indicator parameter), Ip. Excellent results are obtained when all the four parameters (EH, EL, CD and Ip) are used in correlation analysis.     

Donor-enhanced bridge effect on the electronic properties of triphenylamine based dyes: density functional theory investigations

The geometries have been optimized by using density functional theory. The highest occupied molecular orbitals are delocalized on triphenylamine moiety while lowest unoccupied molecular orbital are localized on anchoring group. Intramolecular charge transfer has been observed from highest occupied molecular orbitals to lowest unoccupied molecular orbital. By replacing the vinyl hydrogens with methoxy as well as one benzene ring as bridge leads to a raised energy gap while extending the bridge decreases the energy gap compared to parent molecule. The HOMO energies bump up by extending the bridge. The LUMO energies of all the investigated dyes are above the conduction band of TiO(2) and HOMOs are below the redox couple except 3c. The distortion between anchoring group and triphenylamine can hamper the recombination reaction.     

Prediction of caspase-3 inhibitory activity of 1,3-dioxo-4-methyl-2,3-dihydro-1h-pyrrolo[3,4-c] quinolines: QSAR study

Neurodegenerative disorders are consequences of progressive and irreversible loss of neurons due to unwanted apoptosis which involves caspases, a group of cysteine proteases that cleave other proteins and inactivate them. Among several different groups of caspase enzymes, caspases-3 plays a key role in apoptosis and are a therapeutic target for their inhibition. In pursuit of better caspase-3 inhibitors, a quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c] quinolines as caspase-3 inhibitors using WIN CAChe 6.1 and Medicinal Chemistry Regression Machine. The best QSAR model was selected and validated by internal and external validation method. The values of statistical data are r = 0.955, F = 72.95, SEE = 0.397, q(2) = 0.885, S(PRESS) = 0.44. The present study reveals that when the conformational minimum energy is increased, and lowest unoccupied molecular orbital energy and highest occupied molecular orbital energy are decreased the biological activity can be increased. On the basis of a selected QSAR model, we designed a new series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines compounds, calculated their caspases inhibitory activity and found that the designed compounds were more potent than the existing compounds.     

Prediction of caspase-3 inhibitory activity of 1,3-dioxo-4-methyl-2,3-dihydro-1h-pyrrolo[3,4-c] quinolines: QSAR study

Neurodegenerative disorders are consequences of progressive and irreversible loss of neurons due to unwanted apoptosis which involves caspases, a group of cysteine proteases that cleave other proteins and inactivate them. Among several different groups of caspase enzymes, caspases-3 plays a key role in apoptosis and are a therapeutic target for their inhibition. In pursuit of better caspase-3 inhibitors, a quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c] quinolines as caspase-3 inhibitors using WIN CAChe 6.1 and Medicinal Chemistry Regression Machine. The best QSAR model was selected and validated by internal and external validation method. The values of statistical data are r = 0.955, F = 72.95, SEE = 0.397, q² = 0.885, S_PRESS = 0.44. The present study reveals that when the conformational minimum energy is increased, and lowest unoccupied molecular orbital energy and highest occupied molecular orbital energy are decreased the biological activity can be increased. On the basis of a selected QSAR model, we designed a new series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines compounds, calculated their caspases inhibitory activity and found that the designed compounds were more potent than the existing compounds.     

Theoretical evaluation of inhibition performance of purine corrosion inhibitors

Inhibition mechanism of three purine compounds, adenine (A), 2-amino-6-thiol-9H-purine (B) and 2,6-dithiol-9H-purine (C), was investigated by quantum chemical calculation and molecular dynamic simulation. The molecular reactivity was studied by quantum chemical calculation, and the distribution of the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), the energy gap between HOMO and LUMO and the Fukui index were proposed to describe the active sites of molecules, and the inferred inhibition efficiency followed the order of A < B < C. Furthermore, the adsorption behaviour of these three purine molecules on a metal surface was investigated via molecular dynamics simulation. The analysis of adsorption configuration indicated that these three purine molecules adsorbed parallely onto the metal surface, and the inferred inhibition efficiency from interaction energy also followed the order of A < B < C. These inferred inhibition efficiency from theoretical calculation was in good accordance with experimental results. This accordance indicated that our proposed theoretical method might be a feasible approach to assess the inhibition performance of inhibitors. Moreover, our research was helpful to filter the aimed inhibitor and design of the new inhibitor.