Application of Density Functional Theoretic Descriptors to Quantitative Structure-Activity Relationships with Temperature Constrained Cascade Correlation Network Models of Nitrobenzene Derivatives

IntroductionNitrobenzene derivatives have been used as organ-ic chemical materials and intermediates for many yearsin the chemical industry. Many of those chemicals arereleased into environment and especially into aquaticsystems, and thus have a high pote…     

RPTLC Study of QSRR and QSAR for Some Benzimidazole Derivatives

JPC – Journal of Planar Chromatography – Modern TLC - Quantitative structure–retention relationships (QSRR) and quantitative structure–activity relationships (QSAR) have...     

基于三维分子描述符的埃坡霉素类衍生物抗癌活性预测

为预测埃坡霉素类衍生物的抗癌活性, 定义了一套表征分子形状的描述符, 即K阶形状参数, 并计算了67个表征分子的电子、拓扑和几何结构的分子描述符. 描述符经遗传算法筛选, 用于建立基于支持向量学习机(SVM)的抗癌活性分类模型; 用留一法和5重交叉验证法对SVM模型参数进行了优化. 结果表明模型具有较高的预测性且两种方法得到相近结果, 交叉验证的预测正确率达80.6%; 经筛选后的描述符有30个, 其中含有5个K阶形状参数, 这些描述符对埃坡霉素类衍生物的抗癌活性的模型建立具有比较重要的作用.     

吲哚并喹啉衍生物与G-四链体相互作用的分子模拟研究

G-四链体是富含鸟嘌呤碱基的DNA序列通过氢键相互作用形成的四链螺旋结构. 通过小分子化合物诱导与稳定端粒G-四链体从而抑制端粒酶活性是一种新的抗癌策略. 为了研究一系列吲哚并喹啉衍生物与端粒G-四链体的相互作用, 探究其相互作用模式, 从而为实现基于G-四链体结构的药物合理设计提供依据, 使用分子对接的方法构建了吲哚并喹啉衍生物与G-四链体复合物结构, 在此基础上进行分子动力学模拟, 并使用线性相互作用能(LIE)方法计算了化合物与G-四链体的结合自由能. 结果表明: 化合物与G-四链体的主要相互作用方式由氢键、静电与π-π堆积作用构成, 侧链末端基团类型和侧链的长短是影响相互作用强弱的重要因素. 通过LIE方法计算的结合自由能与实验结果基本吻合, 相关度达到r²＝0.79. 并且, 基于预测的结合模式, 总结了拥有更高活性的新型吲哚并喹啉衍生物应具有的几个结构特征.     

Molecular Modeling and Design of Arylthioindole Derivatives as Tubulin Inhibitors

Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carried out. An optimal 3D-QSAR model from the comparative molecular field analysis （CoMFA） for training set with significant statistical quality （R2=0.898） and predictive ability （q2=0.654） was established. The same model was further applied to predict pIC50 values of the compounds in test set, and the resulting predictive correlation coefficient R2（pred） reaches 0.816, further showing that this CoMFA model has high predictive ability. Moreover, the appropriate binding orientations and conformations of these compounds interacting with tubulin are located by docking study, and it is very interesting to find the consistency between the CoMFA field distribution and the 3D topology structure of active site of tubulin. Based on CoMFA along with docking results, some important factors improving the activities of these compounds were discussed in detail and were summarized as follows： the substituents R3-R5 （on the phenyl ring） with higher electronegativity, the substituent R6 with higher eleetropositivity and bigger bulk, the substituent R7 with smaller bulk, and so on. In addition, five new compounds with higher activities have been designed. Such results can offer useful theoretical references for experimental works.     

基于杯芳烃主体的分子自组装研究进展

分子自组装是超分子化学最重要的研究内容之一. 杯芳烃作为继冠醚、环糊精之后的第三代人工合成受体分子已在分子自组装研究方面取得了重要进展并显示了广泛的应用前景. 主要综述杯芳烃衍生物通过氢键、金属诱导配位、π-π作用、疏水作用等非共价键弱相互作用力在溶液状态、固态和界面的分子自组装方面的研究进展.     

Molecular Modeling of Enantioseparation of Phenylazetidin Derivatives by Cyclodextrins

β-Lactams are one of the most widely used types of antibiotics. As β-lactams are chiral, the enantiomeric separation of these compounds was investigated using cyclodextrins, frequently used as chiral separators. Molecular modeling methods were utilized in order to predict possible enantioseparation of four model compounds. Our results revealed that permethylated β-cyclodextrin is more likely to chirally separate the phenylazetidin derivates than the parent β-cyclodextrin. LC experiments using cyclodextrin as chiral stationary phase in most cases confirmed our prediction; however, more experiments and statistical evaluation of the results are needed in order to judge the prediction power of the molecular dynamic method.     

Quantitative Relationships Between Molecular Descriptors,Chromatographic Retention Behavior,and In Vitro Antituberculosis Activity of Phytol Derivatives

JPC – Journal of Planar Chromatography – Modern TLC - The lipophilic character of phytol derivatives has been studied using reverse-phase planar chromatographic procedures....     

Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect

Diabetes is the most common metabolic disorder in both developing and non-developing countries, and a well-recognized global health problem. The WHO anticipates an increase in cases from 171 million in 2000 to 366 million by 2030. In the present study, we focus on the preparation of pyrimidine derivatives as potential antidiabetic and antimicrobial agents. Thein vivoeffect on total serum glucose concentration, cholesterol and antioxidant activity was assessed in adult male albino Wister rats and compared to the reference drug glimperide. Promising results were observed for compound 5. The histopathological study confirms that compound 5 results in significant activity with liver maintenance. The antimicrobial activities were evaluated against several bacterial strains such as Salmonella typhimurium ATCC 25566, Bacillus cereus, Escherichia coli NRRN 3008, Pseudomonas aeruginosa ATCC 10145, Staphylococcus aureus ATCC 6538and fungi such as Rhizopus oligosporus, Mucor miehei and Asperillus niger. Compounds 4 and 5 showed a good inhibition of the bacterial zone compared to the reference drug cephradine. Finally, we suggest protein targets for these drugs based on computational analysis, and infer their activities from their predicted modes of binding using molecular modeling. The molecular modeling for compounds 4 and 5 resulted in improved docking scores and hydrogen bonding. The docking studies are in good agreement with the in vitro and in vivo studies.     

Crystallography,Molecular Modeling,and COX-2 Inhibition Studies on Indolizine Derivatives

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC₅₀ of 5.84 µM, as compared to indomethacin (IC₅₀ = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 2₁/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)ų. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.     

基于荧光素衍生物单分子器件的二进制全减器和全加器

合成了一种随p H值变化具有5种互变分子结构的新型荧光素衍生物QHF+.通过紫外-可见吸收光谱研究了不同p H值下QHF+发生转化产生的5种结构的特征谱图,并以此为基础设计了二进制逻辑电路.在乙醇/水(体积比为1∶1)混合溶剂体系中,采用等摩尔的H+或OH-作为化学输入信号,选取424和490nm波长下的特定吸光度或透射率作为标准阈值,通过比较紫外-可见吸收光谱的变化,平行实现了多个逻辑门(XOR和INH或AND和XOR)的运算,模拟了二进制全减器和全加器的运行.     

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: −17.65 kcal mol⁻¹ (D6), −18.07 kcal mol⁻¹ (D2), −18.13 (D5) kcal mol⁻¹, and −10.31 kcal mol⁻¹ (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (−12.84 kcal mol⁻¹) and L-tyrosine (−9.04 kcal mol⁻¹) in melanogenesis.     

二茂铁衍生物疏水参数的测定及其保留值与结构定量关系的研究

以甲醇－水为流动相,用反相高效液相色谱法测定了二茂铁衍生物的疏水参数。结果表明,ｌｇｋ’与流动相中有机调节剂的体积百分比成线性关系;理论计算所得的Ｈａｎｓｃｈ的π值、Ｒｅｋｋｅｒ的ｆ值与ｌｇｋｗ相关,且前者与ｌｇｋｗ的相关性较好;二茂铁衍生物的保留值可通过多因素（ｌｇｋｗ、ＨＡ、ＨＤ、Ｈａｎｓｃｈ的π值等）公式预测。同时对二茂铁衍生物和苯系列化合物的碎片参数值作了比较。     

应用量化参数和CoMFA法研究苯甲酸类化合物的结构和其pKa值的相关性

人工神经网;应用量化参数和CoMFA法研究苯甲酸类化合物的结构和其pKa值的相关性