Search Results (6)

This paper examines the quantitative structure–inhibitory activity relationship of 15-lipoxygenase (15-LOX) in sets of 100 homo- and heterocyclic compounds using GUSAR 2019 software. Statistically significant valid models were built to predict the IC50 parameter. A combination of MNA and QNA descriptors with three whole molecular descriptors (topological length, topological volume and lipophilicity) was used to develop 18 statistically significant, valid consensus QSAR models. These compounds showed varying degrees of inhibition of the catalytic activity of 15-LOX: the range of variation in the pIC₅₀ value was 3.873. The satisfactory coincidence between the theoretically calculated and experimentally determined pIC₅₀ values for compounds TS1, TS2 and 1–8 suggests the potential use of models M1–M18 for the virtual screening of virtual libraries and databases to find new potentially efficient inhibitors of 15-LOX. Full article

A quantitative analysis of the relationship between the structure and inhibitory activity against the herpes simplex virus thymidine kinase (HSV-TK) was performed for the series of 5-ethyluridine, N2-guanine, and 6-oxopurines derivatives with pronounced anti-herpetic activity (IC₅₀ = 0.09 ÷ 160,000 μmol/L) using the GUSAR 2019 software. On the basis of the MNA and QNA descriptors and whole-molecule descriptors using the self-consistent regression, 12 statistically significant consensus models for predicting numerical pIC₅₀ values were constructed. These models demonstrated high predictive accuracy for the training and test sets. Molecular fragments of HSV-1 and HSV-2 TK inhibitors that enhance or diminish the anti-herpetic activity are considered. Virtual screening of the ChEMBL database using the developed QSAR models revealed 42 new effective HSV-1 and HSV-2 TK inhibitors. These compounds are promising for further research. The obtained data open up new opportunities for developing novel effective inhibitors of TK. Full article

The present work addresses the quantitative structure–antioxidant activity relationship in a series of 148 sulfur-containing alkylphenols, natural phenols, chromane, betulonic and betulinic acids, and 20-hydroxyecdysone using GUSAR2019 software. Statistically significant valid models were constructed to predict the parameter logk₇, where k₇ is the rate constant for the oxidation chain termination by the antioxidant molecule. These results can be used to search for new potentially effective antioxidants in virtual libraries and databases and adequately predict logk₇ for test samples. A combination of MNA- and QNA-descriptors with three whole molecule descriptors (topological length, topological volume, and lipophilicity) was used to develop six statistically significant valid consensus QSPR models, which have a satisfactory accuracy in predicting logk₇ for training and test set structures: R²_TR > 0.6; Q²_TR > 0.5; R²_TS > 0.5. Our theoretical prediction of logk₇ for antioxidants AO1 and AO2, based on consensus models agrees well with the experimental value of the measure in this paper. Thus, the descriptor calculation algorithms implemented in the GUSAR2019 software allowed us to model the kinetic parameters of the reactions underlying the liquid-phase oxidation of organic hydrocarbons. Full article

A simple method for the synthesis of new derivatives of isoindoline-1,3-dione is developed in this study, which consists of the interaction of N-arylbenzenecarboximidamides with phthalic anhydride in benzene at reflux. It was found that carrying out the reaction without heating leads to the formation of monoacylation products—phthalic acid amides. The structure of the isolated substances was proved using ¹H and ¹³C NMR spectroscopy. Acute toxicity and biological activity in silico were studied for all of the obtained compounds using the online programs GUSAR and PASS. For 2-(phenyl(phenylimino)methyl)isoindoline-1,3-dione and 2-((phenyl(phenylimino)methyl)carbamoyl)benzoic acid, an acute toxicity and biological activity in vivo was studied in laboratory mice. It was shown that the results of in silico and in vivo methods are comparable and indicate the low toxicity of the obtained compounds. It was revealed that 2-(phenyl(phenylimino)methyl)isoindoline-1,3-dione has a high analgesic activity, 1.6 times higher than the activity of the reference drug metamizole sodium. Full article

Using the GUSAR 2013 program, the quantitative structure–antioxidant activity relationship has been studied for 74 phenols, aminophenols, aromatic amines and uracils having lgk₇ = 0.01–6.65 (where k₇ is the rate constant for the reaction of antioxidants with peroxyl radicals generated upon oxidation). Based on the atomic descriptors (Quantitative Neighborhood of Atoms (QNA) and Multilevel Neighborhoods of Atoms (MNA)) and molecular (topological length, topological volume and lipophilicity) descriptors, we have developed 9 statistically significant QSAR consensus models that demonstrate high accuracy in predicting the lgk₇ values for the compounds of training sets and appropriately predict lgk₇ for the test samples. Moderate predictive power of these models is demonstrated using metrics of two categories: (1) based on the determination coefficients R² (R²_TSi, R²₀, Q²(_F1), Q²(_F2), $\overline{{\mathrm{R}}_{\mathrm{mTSi}}^2}$) and based on the concordance correlation coefficient (CCC)); or (2) based on the prediction lgk₇ errors (root mean square error (RMSEP), mean absolute error (MAE) and standard deviation (S.D.)) The RBF-SCR method has been used for selecting the descriptors. Our theoretical prognosis of the lgk₇ for 8-PPDA, a known antioxidant, based on the consensus models well agrees with the experimental value measure in the present work. Thus, the algorithms for calculating the descriptors implemented in the GUSAR 2013 program allow simulating kinetic parameters of the reactions underling the liquid-phase oxidation of hydrocarbons. Full article

We evaluated the antimicrobial activity of thirty-one nitrogen-containing 5-α-androstane derivatives in silico using computer program PASS (Prediction of Activity Spectra for Substances) and freely available PASS-based web applications (such as Way2Drug). Antibacterial activity was predicted for 27 out of 31 molecules; antifungal activity was predicted for 25 out of 31 compounds. The results of experiments, which we conducted to study the antimicrobial activity, are in agreement with the predictions. All compounds were found to be active with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values in the range of 0.0005–0.6 mg/mL. The activity of all studied 5-α-androstane derivatives exceeded or was equal to those of Streptomycin and, except for the 3β-hydroxy-17α-aza-d-homo-5α-androstane-17-one, all molecules were more active than Ampicillin. Activity against the resistant strains of E. coli, P. aeruginosa, and methicillin-resistant Staphylococcus aureus was also shown in experiments. Antifungal activity was determined with MIC and MFC (Minimum Fungicidal Concentration) values varying from 0.007 to 0.6 mg/mL. Most of the compounds were found to be more potent than the reference drugs Bifonazole and Ketoconazole. According to the results of docking studies, the putative targets for antibacterial and antifungal activity are UDP-N-acetylenolpyruvoylglucosamine reductase and 14-α-demethylase, respectively. In silico assessments of the acute rodent toxicity and cytotoxicity obtained using GUSAR (General Unrestricted Structure-Activity Relationships) and CLC-Pred (Cell Line Cytotoxicity Predictor) web-services were low for the majority of compounds under study, which contributes to the chances for those compounds to advance in the development. Full article