Neural Network Modeling of the Multitarget Rage Inhibitory Activity

Vassiliev, Pavel; Spasov, A. A.; Yanaliyeva, L. R.; Kochetkov, A. N.; Vorfolomeyeva, V. V.; Klochkov, Vladlen; Appazova, D. T.

doi:10.1134/s1990750819030107

Cited by 10 publications

(3 citation statements)

References 7 publications

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“…Through a previously developed technique [25], three most valid experimental 3D models of the indicated Homo sapiens proteins were found: 3OZ0 for PPARD, 4PHU for FFAR1, and 3G0B for DPP4 [26]. The biotargets are grouped by mechanism of action.…”

Section: In Silico Analysismentioning

confidence: 99%

Bornyl Derivatives of p-(Benzyloxy)Phenylpropionic Acid: In Vivo Evaluation of Antidiabetic Activity

et al. 2020

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A series of bornyl derivatives of p-(benzyloxy)phenylpropionic acid were prepared, and their hypoglycemic activities were examined by an oral glucose tolerance test in mice. The results of this test revealed two compounds, 1 and 3, that can reduce the blood level of glucose similarly to reference compound vildagliptin. Both compounds were tested in an experiment on mice with metabolic disorders: the C57BL/6Ay strain. Along with hypoglycemic properties, the two compounds showed different abilities to correct lipid metabolism disorders. In silico prediction revealed that the studied substances are most likely bifunctional multitarget hypoglycemic compounds whose mechanism of action is based on a pronounced reduction in insulin resistance and a strong incretin-mimetic effect. The difference in the size of effects of these compounds on biochemical parameters of blood in the experiment on C57BL/6Ay mice was in good agreement with the computational prediction of the priority ranking of biological targets for these compounds. These results indicate that bornyl derivatives of p-(benzyloxy)phenylpropionic acid have a good potential as new agents for diabetes mellitus treatment due to their hypoglycemic and lipid-normalizing properties.

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Section: In Silico Analysismentioning

confidence: 99%

Bornyl Derivatives of p-(Benzyloxy)Phenylpropionic Acid: In Vivo Evaluation of Antidiabetic Activity

et al. 2020

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“…Search for valid 3D-models of the most abundant α1-β2-γ2-GABA A subtype receptor and 5-HT 2A receptor of Homo sapiens was conducted using a previously developed method [ 39 ]. For each biotarget, three such models were found: for the GABA A receptor, two experimental 6D6T, 6D6U [ 40 ] and one theoretical [ 41 ], for the 5-HT 2A receptor also two experimental 6A93, 6A94 [ 40 ] and one theoretical 5d6b98e9e00432ae919177b2b38d636c [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

“…Ensemble docking was performed using the AutoDockVina 1.1.2 program [ 43 ], each compound in 10 conformers, 5 times in each site of each model, with the calculation of 150 obtained values of the minimum docking energies ΔE, as described in [ 39 ]. The binding mechanism was analyzed using the LigandScout 4.1 program [ 44 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Pharmacological Evaluation of Novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole Derivatives as Promising Anxiolytic and Analgesic Agents

et al. 2021

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A number of novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole derivatives 2 were obtained by alkylation mainly in the 1H-tautomeric form of 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole or its 8,9-dimethyl-substituted analog 4-chlorobenzyl bromide, 4-chloroacetic acid fluoroanilide, and 4-tert-butylphenacyl bromide in neutral medium. Compounds 3 were cyclized and synthesized earlier with 11-phenacyl-substituted diazepino[1,2-a]benzimidazoles upon heating in conc. HBr. The chemical structures of the compounds were clarified by using the 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR) technique. Anxiolytic properties were evaluated using the elevated plus maze (EPM) and open field (OF) tests. The analgesic effect of compounds was estimated with the tail flick (TF) and hot plate (HP) methods. Besides, possible the influence of the test compounds on motor activities of the animals was examined by the Grid, Wire, and Rotarod tests. Compounds 2d and 3b were the most active due to their prominent analgesic and anxiolytic potentials, respectively. The results of the performed in silico analysis showed that the high anxiolytic activity of compound 3b is explained by the combination of a pronounced interaction mainly with the benzodiazepine site of the GABAA receptor with a prominent interaction with both the specific and allosteric sites of the 5-HT2A receptor.

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Neural network modeling search for multitarget RAGE inhibitors with different target activity spectra

2021

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Neural Network Modeling of the Multitarget Rage Inhibitory Activity

Cited by 10 publications

References 7 publications

Bornyl Derivatives of p-(Benzyloxy)Phenylpropionic Acid: In Vivo Evaluation of Antidiabetic Activity

Bornyl Derivatives of p-(Benzyloxy)Phenylpropionic Acid: In Vivo Evaluation of Antidiabetic Activity

Synthesis and Pharmacological Evaluation of Novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole Derivatives as Promising Anxiolytic and Analgesic Agents

Neural network modeling search for multitarget RAGE inhibitors with different target activity spectra

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