Quantitative Structure–Activity Relationship (QSAR) Analysis of the Cytotoxicities Of Aminohydroxyguanidine Derivatives and Their Antiviral Activities in Vitro

Substituted Schiff bases of l-amino-3-hydroxyguanidine (SB-HAG) were tested for the first time against noninfected T4 lymphocytes (CEM-6 cells) and the same cell line infected by HIV-1 in vitro. Twenty-one of 23 compounds at micromolar levels did not inhibit the growth of the noninfected T4 cells, suggesting minimal cytotoxicity. The antiviral effects of these compounds in a micromolar concentration range have been shown to be nonsignificant (<30%) against HIV-1. Three-dimensional parameter focusing of the physicochemical properties (i.e., log P and V _w) and the marginal antiviral activities shows that the marginally active compounds lie in a region different from the inactive compounds. QSAR analysis of the two subsets shows that the cytotoxicity correlates well with the electronic and lipophilic parameters. The results of the QSAR analysis can serve as guidelines for further structural modification of this series of compounds to minimize the cytotoxicity against host cells.     

吡啶并嘧啶类衍生物抗癌活性与电子结构关系的量子化学研究

采用量子化学密度泛函理论(DFT)方法,在B3LYP/6-31G*基组水平上对吡啶并嘧啶类衍生物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吡啶并嘧啶类衍生物抗癌活性与电子结构的构效关系,结果表明:吡啶并嘧啶类衍生物抗癌活性与最低空轨道的能量,分子的偶极矩、苯环上5位碳原子的电荷密度及苯环上总电荷密度相关。     

以基团为基准借电负性修正的分子距边矢量对N，N-二甲基-2-溴苯乙胺类衍生物进行结构表征和活性预测

以基团为基准并借助电负性修正分子距边矢量 (VMDE) ,对N ,N 二甲基 2 溴苯乙胺类衍生物的结构进行表征 ,然后用多元线性回归技术 (MLR)建立新分子距边矢量与其生物活性的相关关系 ,结果表明 :新分子距边矢量与生物活性之间有良好的线性关系 ,复相关系数高达R =0 96 75 ,均方根误差RMS =0 140 ,解释方差EV =0 96 19,统计量F =87 8,优于文献使用常规取代基参数获得的结果 :R =0 917,S =0 2 38,F =5 0 1.为检查模型的稳定性和预测能力 ,还作了随机抽样检验和交互校验 ,结果优良     

靛玉红衍生物结构与抗肿瘤活性关系预测方程的建立

目的：建立一个方程,用于预测靛玉红衍生物（主要为靛玉红-3′-肟类）的体外抗肿瘤活性。方法：采用经典的二维定量构效关系研究方法,对24个靛玉红衍生物进行计算机模拟与统计分析。结果：得到靛玉红衍生物体外抗肿瘤活性的定量构效方程,且发现,该类靛玉红衍生物的活性与脂水分配系数、偶极矩、总电荷绝对值和最大负电荷呈负相关,与分子体积呈正相关。结论：所得方程能有效预测该类靛玉红衍生物的活性,且对其类似物的设计与改造具有指导意义。     

Synthesis and In Vitro Antioxidant Activity of New 3-Substituted-2-Oxindole Derivatives

A series of new 1,3-dihydro-3-hydroxy-3-(2-phenyl-2-oxoethyl)-2H-indol-2-ones (1a-g) and 1,3-dihydro-3-(2-phenyl-2-oxoethylidene)-2H-indol-2-ones (2a-g) were synthesised by Knoevenagel condensation of substituted indole-2,3-diones (isatins) with various acetophenones. The synthesised compounds were characterised by their physical data, elemental, IR, ¹H NMR, ¹³C NMR and mass spectral analyses and their in vitro antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay. These compounds showed moderate to good antioxidant activities as compared with the standard, ascorbic acid. The antioxidant potential of 3-hydroxy-3-substituted oxindoles (1a-g) increased in a concentration-dependent manner from 10 to 500 μg/ml with 5-fluoro and 5-methyl analogues showing maximum activity. Of 3-aroyl methylene indol-2-ones (2a-g), majority of compounds with halogen substitution at position 5 of isatin ring exhibited good antioxidant activity within a concentration range of 5-100 μg/ml and the maximum activity was observed at 20 and 25 μg/ml concentrations. Thus, our study provides evidence that some newly synthesised isatin derivatives exhibit substantial antioxidant activity at low concentrations.     

N-〔3-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-2-羟基-丙基〕-氨基乙酸及其衍生物的合成和抗真菌活性

设计合成了Ｎ〔３（１Ｈ１，２，４三唑１基）２（２，４二氟苯基）２羟基丙基〕氨基乙酸及其９个衍生物，均为未见文献报道的新化合物，初步药理试验表明：部分化合物对浅部真菌有一定的活性，除卡氏枝孢霉菌外，对其它深部真菌活性较弱，其中化合物（５ｅ），（５ｈ）对某些真菌的体外活性较强，明显优于氟康唑，但稍弱于酮康唑     

Comparison of AM1 and B3LYP-DFT for inhibition of MAO-A by phenylisopropylamines: a QSAR study

The aim of this study is to provide an initial indication regarding the scope and limitations of some state-of-the-art methods in computational chemistry, including semiempirical (AM1) and density functional theory (B3LYP), in the flip regression procedure applied to the inhibition of phenylisopropylamines. The results show that the models established based on the density functional theory-B3LYP are better than that based on semiempirical method (AM1). It is demonstrated that electron-rich ring systems and highest occupied molecular orbital levels tended to increase activity. In this contribution, it is shown that the orientation of nodes in their occupied pi orbitals, and also the energies of these orbitals explain a further large portion of the variance in their inhibitory activity.     

Exploring QSARs for Inhibitory Activity of Non-peptide HIV-1 Protease Inhibitors by GA-PLS and GA-SVM

The support vector machine (SVM) and partial least square (PLS) methods were used to develop quantitative structure activity relationship (QSAR) models to predict the inhibitory activity of non-peptide HIV-1 protease inhibitors. Genetic algorithm (GA) was employed to select variables that lead to the best-fitted models. A comparison between the obtained results using SVM with those of PLS revealed that the SVM model is much better than that of PLS. The root mean square errors of the training set and the test set for SVM model were calculated to be 0.2027, 0.2751, and the coefficients of determination (R²) are 0.9800, 0.9355 respectively. Furthermore, the obtained statistical parameter of leave-one-out cross-validation test (Q²) on SVM model was 0.9672, which proves the reliability of this model. The results suggest that TE2, Ui, GATS5e, Mor13e, ATS7m, Ss, Mor27e, and RDF035e are the main independent factors contributing to the inhibitory activities of the studied compounds.     

苯并咪唑衍生物的抗肿瘤活性及构效关系研究

恶性肿瘤是严重威胁人类生命健康的疾病,随着其发病率和死亡率的不断上升,对抗肿瘤药物的开发提出了巨大的需求.作为核酸类似物的苯并咪唑衍生物,具有广谱的抗肿瘤活性,是抗肿瘤药物的优势骨架.近年来研究表明苯并咪唑衍生物对肝癌、肺癌、乳腺癌、肾癌、前列腺癌、宫颈癌等多种肿瘤细胞有良好的抗肿瘤效果.本文综述了苯并咪唑类衍生物与肿...