Aconitum and delphinium diterpenoid alkaloids of local anesthetic activity: comparative QSAR analysis based on GA-MLRA/PLS and optimal descriptors approach.

The duration of anesthesia (related to protein binding of a drug) and the onset time (determined by the pKa) are important characteristics in assessment of local anesthetic agents. They are known to be affected by a number of factors. Early studies of antiarrhythmic diterpenoid alkaloids from plants Aconitum and Delphinium suggested that they possess local anesthetic activity due to their ability to suppress sodium currents of excited membranes.

Immunotoxicity of nanoparticles: a computational study suggests that CNTs and C60 fullerenes might be recognized as pathogens by Toll-like receptors.

Over the last decade, a great deal of attention has been devoted to study the inflammatory response upon exposure to multi/single-walled carbon nanotubes (CNTs) and different fullerene derivatives. In particular, carbon nanoparticles are reported to provoke substantial inflammation in alveolar and bronchial epithelial cells, epidermal keratinocytes, cultured monocyte-macrophage cells, etc. We suggest a hypothetical model providing the potential mechanistic explanation for immune and inflammatory responses observed upon exposure to carbon nanoparticles.

Receptor- and ligand-based study of fullerene analogues: comprehensive computational approach including quantum-chemical, QSAR and molecular docking simulations.

Fullerene and its derivatives have potential antiviral activity due to their specific binding interactions with biological molecules. In this study fullerene derivatives were investigated by the synergic combination of three approaches: quantum-mechanical calculations, protein-ligand docking and quantitative structure-activity relationship methods. The protein-ligand docking studies and improved structure-activity models have been able both to predict binding affinities for the set of fullerene-C60 derivatives and to help in finding mechanisms of fullerene derivative interactions with human immunodeficiency virus type 1 aspartic protease, HIV-1 PR.

Use of quantitative structure-enantioselective retention relationship for the liquid chromatography chiral separation prediction of the series of pyrrolidin-2-one compounds.

In this work, the enantioseparation of 15 structurally similar chiral solutes is studied, and analysis of the retention factors is performed using a genetic algorithm and multiple linear regression analysis technique. The present quantitative structure-enantioselective retention relationship model generated for retention factors' data has confirmed the importance of a number of descriptors altering the retention behavior and enantioselectivity of the studied compounds. Thus, fragment-based descriptor PSA, which encodes polar surface area, has confirmed the crucial role of heteroatoms in the retention behavior exhibited by pyrroliddin-2-ones.

Structure-activity relationship investigations of leishmanicidal N-benzylcytisine derivatives.

In vitro leishmanicidal activity of 16 N-benzylcytisine derivatives has been evaluated using Leishmania donovani axenic amastigotes. In general, halogen (bromo-, chloro-) derivatives appeared to be more toxic against parasites than their parent compounds. Quantum-chemical calculations helped to recognize certain patterns in the structure of frontier orbitals related to bioactivity of compounds.

Aconitum and Delphinium alkaloids of curare-like activity. QSAR analysis and molecular docking of alkaloids into AChBP.

Early studies have shown that some of diterpenoid alkaloids, found in highly toxic plants of the genera Aconitum and Delphinium, act at neuronal nicotinic acetylcholine receptors (nAChRs) and exhibit potent N-cholinolytic activity. In the current study, GA-MLRA and GA-PLS approaches have been used to build QSAR models to predict N-cholinolytic activity measured in vivo (blockade of neuromuscular conductivity, BNMC and third eyelid relaxing activity, TYRA) and in vitro (suppression of frog's abdominal straight muscles on acetylcholine, SAM) for a series of diterpenoid alkaloids. Random splitting of a data set (five trials in total) produced QSAR models of a good level of correlation between experimental in vitro/in vivo and calculated N-cholinolytic activity expressed as log(1/ED(50)) with following average statistical parameters: log BNMC (r(2) = 0.

Aconitum and Delphinium alkaloids "Drug-likeness" descriptors related to toxic mode of action.

Large series of Aconitum and Delphinium alkaloids have been investigated by means of QSAR analysis. Descriptors related to "drug-likeness" of molecules were selected to discriminate between "drugs" and "non-drugs" amongst diterpenoid alkaloids of interest. A usefulness of such approach has been assessed and it proved to give reliable results on whether a particular diterpenoid alkaloid is likely to be either poison or drug.

Aconitum and Delphinium sp. alkaloids as antagonist modulators of voltage-gated Na+ channels. AM1/DFT electronic structure investigations and QSAR studies.

Early pharmacological studies of Aconitum and Delphinium sp. alkaloids suggested that these neurotoxins act at site 2 of voltage-gated Na(+) channel and allosterically modulate its function. Understanding structural requirements for these compounds to exhibit binding activity at voltage-gated Na(+) channel has been important in various fields.

A QSAR toxicity study of a series of alkaloids with the lycoctonine skeleton.

A QSAR toxicity analysis has been performed for a series of 19 alkaloids with the lycoctonine skeleton. GA-MLRA (Genetic Algorithm combined with Multiple Linear Regression Analysis) technique was applied for the generation of two types of QSARs: first, models containing exclusively 3D-descriptors and second, models consisting of physicochemical descriptors. As expected, 3D-descriptor QSARs have better statistical fits.