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Inhibition of NADH dehydrogenase (Complex I) of the mitochondrial respiratory chain by 1-methyl-4-phenylpyridinium (MPP') and its analogs results in dopaminergic cell death. In the present study, the inhibition of mitochondrial respiration and of NADH oxidation in inverted inner membrane preparations by the oxidation products of N-methyl-stilbazoles (N-methyl-styrylpyridiniums) are characterized. These nonflexible MPP' analogs were found to be considerably more potent inhibitors than the corresponding MPP' derivatives. The IC,, values for these compounds and previously published figures for MPP+ analogs were then used to select a computer model based on structural parameters to predict the inhibitory potency of other compounds that react at the "rotenone site" in Complex I. A series of 12 novel inhibitors different in structure from the basic set were used to test the predictive capacity of the models selected. Despite major structural differences between the novel test compounds and the MPP+ and styrylpyridinium analogs on which the models were based, substantial agreement was found between the predicted and experimentally determined IC, values. The value of this technique lies in the potential for the prediction of the inhibitory potency of other drugs and toxins which block mitochondrial respiration by interacting at the rotenone sites. 0

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To study the relation between the structure of a compound and its properties is one of the fundamental trends in chemistry and materials science. A classic example is the well-known influence of the structures of diamond and graphite on their physicochemical properties, in particular, hardness. However, some other properties of these allotropic modifications of carbon, e.g., fractal properties, are poorly understood. In this work, the spatial series (interatomic distance histograms) calculated using the crystal structures of diamond and graphite are investigated. Hurst exponents H are estimated using detrended fluctuation analysis and power spectral density. The values of H are found to be 0.27–0.32 and 0.37–0.42 for diamond and graphite, respectively. The calculated data suggest that the spatial series have long memory with a negative correlation between the terms of the series; that is, they are antipersistent.

29 conjugates of methylene blue and four chemical structures, including derivatives of carbazole, tetrahydrocarbazole, substituted indoles and γ-carboline, combined with a 1-oxopropylene spacer have been studied as channel blockers of the NMDA receptor (binding site of MK-801) by using four QSAR methods (multiple linear regression, random forest, support vector machine, Gaussian process) and molecular docking. QSAR models have satisfactory characteristics. The analysis of regression models at the statistical level revealed an important role of the hydrogen bond in the complex formation. This was also confirmed by the study of modeled by docking complexes. It was found that the increase in the inhibitory activity of the part of compounds could be attributed to appearance of additional H bonds between the ligands and the receptor.