QUANTUM CHEMICAL AND PHARMACOLOGICAL CHARACTERISTICS OF 6-ARYLAMINO-7H-[1,2,4]TRIAZOLO[3,4-B][1,3,4]THIADIAZINES DERIVATIVES
DOI:
https://doi.org/10.58407/bht.2.25.8Keywords:
6-arylamino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine, quantum chemical descriptors, pharmacological activity, correlation analysis, prediction of metabolitesAbstract
Purpose of the work. To determine the relationship between biological activity and quantum chemical descriptors for 6-arylamino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives and to predict their metabolic pathways.
Methodology. For the primary screening, a library of compounds containing 42 derivatives of 6-arylamino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine was created.
The study was conducted using ChemOffice software package, Molinspiration Cheminformatics, OSIRIS Property Explorer, SwissTargetPrediction, SuperPred, and ProTox online resources. The energy characteristics, pharmacokinetic parameters, and toxicity were calculated, compliance with the Lipinski rule was assessed, and the probable ligand proteins were predicted. Microsoft Excel was used to perform linear correlation and regression analyses in the coordinates of binding probability – quantum chemical descriptors.
Scientific novelty. Virtual screening of pharmacological activity and probable metabolic products for new 6-arylamino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives was performed and correlations between the probability of binding to Histone deacetylase 4 and Cyclin-dependent kinase 2/cyclin A proteins and energy parameters of the molecules were revealed.
Conclusions. Prediction of possible biological activity for a number of 6-arylamino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives was performed. A number of correlation dependencies were established for the probable ligands with the highest binding probability and energies of the highest occupied and lowest vacant molecular orbitals. The metabolic pathways with the formation of hydroxylated, demethylated, and O- and N-acylated forms of the starting compounds were predicted. The obtained results are useful for a more reasonable virtual screening of biological activity of new 6-arylamino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives for the targeted synthesis of future medicinal substances.
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