Antiviral agents towards Chikungunya virus: structures, syntheses, and isolation from natural sources

© Springer Nature Singapore Pte Ltd. 2017. Emerging variants of known RNA viruses present an increasing threat to mankind worldwide through their enlarging impact on morbidity and mortality. One of them is the chikungunya disease, which becomes a major public health problem and economic threat. Current world has no approved antiviral drugs available against chikungunya infection. This Book Chapter mainly focuses on discussion of the antiviral compounds that have been reported to inhibit chikungunya virus replication. Various syntheses of antiviral agents, compounds isolated from natural sources, and some structure-activity relationships are illustrated.status: publishe

Sulfonamide Molecular Crystals: Structure, Sublimation Thermodynamic Characteristics, Molecular Packing, Hydrogen Bonds Networks

The crystal structures of ten sulfonamides have been determined by X-ray diffraction. On the basis of our previous data, the obtained results and literature data crystal properties including molecular conformational states, packing architecture, and hydrogen bond networks were comparatively analyzed using graph set notations. Conformational flexibility of the bridge connecting two phenyl rings was studied. It was found out that the most frequently occurring graphs for compounds with a single hydrogen bond are infinite chains with four atoms included. The molecular packing architecture of the selected crystals may be conditionally divided into three different groups. The idea underlying such classification is the difference in structure and composition of molecular layers that can be singled out for most packings. The influence of various molecular fragments on crystal lattice energy was analyzed. A correlation between melting points and fragmental molecular interactions in the crystal lattices was obtained. The thermodynamic aspects of the sulfonamide sublimation were studied by determining the temperature dependence of vapor pressure using the transpiration method. A correlation between the Gibbs energy of the sublimation process and the melting points was found. Besides, a regression equation was derived to describe the correlation between the sublimation entropy terms and crystal density data calculated from X-ray diffraction results

Calculation of Aqueous Solubility of Crystalline Un-Ionized Organic Chemicals and Drugs Based on Structural Similarity and Physicochemical Descriptors

Solubilities of crystalline organic compounds calculated according to AMP (arithmetic mean property) and LoReP (local one-parameter regression) models based on structural and physicochemical similarities are presented. We used data on water solubility of 2615 compounds in un-ionized form measured at 25 ± 5 °C. The calculation results were compared with the equation based on the experimental data for lipophilicity and melting point. According to statistical criteria, the model based on structural and physicochemical similarities showed a better fit with the experimental data. An additional advantage of this model is that it uses only theoretical descriptors, and this provides means for calculating water solubility for both existing and not yet synthesized compounds

Physicochemical property profile for brain permeability: comparative study by different approaches

<p>A comparative study of classification models of brain penetration by different approaches was carried out on a training set of 1000 chemicals and drugs, and an external test set of 100 drugs. Ten approaches were applied in this work: seven medicinal chemistry approaches (including “rule of 5” and multiparameter optimization) and also three SAR techniques: logistic regression (LR), random forest (RF) and support vector machine (SVM). Forty-one different medicinal chemistry descriptors representing diverse physicochemical properties were used in this work. Medicinal chemistry approaches based on the intuitive estimation of preference zones of CNS or non-CNS chemicals, with different rules and scoring functions, yield unbalanced models with poor classification accuracy. RF and SVM methods yielded 82% and 84% classification accuracy respectively for the external test set. LR was also successful in CNS/non-CNS (denoted in this study as CNS+/CNS−) classification and yielded an overall accuracy equivalent to that of SVM and RF. At the same time, LR is especially valuable for medicinal chemists because of its simplicity and the possibility of clear mechanistic interpretation.</p