Chemometric QSAR studies of antifungal azoxy compounds

Summary Quantitative structure-activity relationships (QSARs) for 16 azoxy compounds with antifungal activity have been studied by the combined approach of a partial least-squares method and factorial design. The PLS model equation suggested the structural requirements of two substituents, R₁ and R₂, for the antifungal activity. The sterically bulky and hydrophobic R₁ substituents and electron-withdrawing R₂ substituents are favorable for the activity. We propose candidate compounds which are more potent than the compounds based on QSAR data. In this study, we show that the chemometric approach is a powerful tool for QSAR studies and drug design.Abbreviations PLS partial least squares - FD factorial design - MLR multiple linear regression - PPs principal properties     

QSAR and Mechanistic studies on the genotoxic compounds including environmental effects

The effects of a proximate condensed environment as the solvent and cellular structured patterns (biopolymers, membranes, etc.) play an important role in determination of the courses of molecular processes in biology. We present here the background of methods developed for such an environmental effects estimation combining the continuum and discrete models. Their applications within theoretical studies into the mechanisms of carcinogenic action of alkylating N-nitrosocompounds are shown. The results given cover four different areas, namely the quantitative structure-activity relationship, mechanistic studies into their metabolic activation reactions, interactions of the ultimate carcinogens with DNA, and finally their genetic consequences.     

Potential of radioiodinated anti cancer compounds of natural origin for cancer therapy

Plumbagin and Quercetin are naturally occurring compounds which exhibit anti-cancerous activity. To evaluate the effect of radioiodination on cytotoxicity, both Plumbagin and Quercetin were radioiodinated with ¹²⁵I ¹²⁵I-Plumbagin and ¹²⁵I-Quercetin could be prepared in moderate yields and good radiochemical purity and were charactenzed using reverse phase HPLC. In Swiss mice bearing fibrosarcoma, ¹²⁵I-Plumbagin showed a tumor uptake of ∼2.5%ID/g at 3 h p.i. and ∼0.5% ID/g at 24 h p.i. on i.v. injection. When injected intratum orally, greater tumor uptake and retention was observed (∼20%ID/g at 3 h p.i. and ∼14%ID/g at 24 h p.i. respectively).     

Piecewise hypersphere modeling by particle swarm optimization in QSAR studies of bioactivities of chemical compounds

As the structural diversity in a quantitative structure-activity relationship (QSAR) model increases, constructing a good model becomes increasingly difficult, and simply performing variable selection might not be sufficient to improve the model quality to make it practically usable. To combat this difficulty, an approach based on piecewise hypersphere modeling by particle swarm optimization (PHMPSO) is developed in this paper. It treats the linear models describing the sought-for subsets as hyperspheres which have different radii in the data space. According to the attribute of each hypersphere, all compounds in the training set are allocated to hyperspheres to construct submodels, and particle swarm optimization (PSO) is applied to search the optimal hyperspheres for finding satisfactory piecewise linear models. A new objective function is formulated to determine the appropriate piecewise models. The performance is assessed using three QSAR data sets. Experimental results have shown the good performance of this technique in improving the QSAR modeling.     

苯胺衍生物式电位的QSAR研究

以AM1量子化学半经验分子轨道方法计算22个苯胺衍生物的分子结构参数,用多元线性回归的方法研究了13个式电位已知的苯胺衍生物的氧化式电位与其分子结构参数之间的关系.苯胺衍生物式电位与离子化电势(Ip),N原子上的净电荷(e(N),总的偶极矩(μt)和第四个碳上的净电荷(e(C4))有很好的相关性,回归方程为:E0′=-7.820 5 0.884 9(Ip-3.739(e(N)-0.093 56μt 0.925 1(e(C4)),(R=0.979,SD为0.023 6).依据回归方程合理地预测了其余9个苯胺衍生物的离子化电势和式电位,探讨了取代基性质和取代位置对离子化电势和式电位的影响.     

3-D QSAR studies on histone deacetylase inhibitors. A GOLPE/GRID approach on different series of compounds

Docking simulation and three-dimensional quantitative structure-activity relationships (3D-QSARs) analyses were conducted on four series of HDAC inhibitors. The studies were performed using the GRID/GOLPE combination using structure-based alignment. Twelve 3-D QSAR models were derived and discussed. Compared to previous studies on similar inhibitors, the present 3-D QSAR investigation proved to be of higher statistical value, displaying for the best global model r2, q2, and cross-validated SDEP values of 0.94, 0.83, and 0.41, respectively. A comparison of the 3-D QSAR maps with the structural features of the binding site showed good correlation. The results of 3D-QSAR and docking studies validated each other and provided insight into the structural requirements for anti-HDAC activity. To our knowledge this is the first 3-D QSAR application on a broad molecular diversity training set of HDACIs.     

硝基芳烃对梨形四膜虫急性毒性的定量构效关系研究

硝基芳烃衍生物是炸药、染料、农药和有机合成的重要原料或中间体,应用极为广泛,但它们均为有毒物质,是我国松花江中主要有机污染物之一,其中有些化合物已被美国环保局列为优先监测污染物[1].     

Recent advances on heterocyclic compounds with antiviral properties

Chemistry of Heterocyclic Compounds - In recent years several important viral infections have emerged and antiviral chemotherapeutic agents are not sufficiently effective in clinic, leading to...     

QSAR studies on anti-apoptotic Bcl-2 protein inhibitors

QSAR studies on a series of inhibitors for anti-apoptotic Bcl-2 proteins based on BHI-1 were performed the activities are found to correlate well with some topological parameters and steric parameters. The results are critically discussed on the basis of regression data, Pogliani factor Q and cross validation technique. The results are found to be useful in discussing the mechanism of drug–receptor interaction.     

Synthesis and QSAR studies on thiazolidinones as anti-HIV agents

Selected 4-thiazolidinone have been synthesized and tested as anti-HIV activity. The results of the in vitro tests showed that one of the compounds, 5, inhibited the enzyme at 0.204 microM concentration with minimal toxicity to MT-4 cell. Furthermore, the QSAR studies indicated the role of PMIZ, Ovality and Total energy content of the compounds in rationalizing the activity.