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Information × Registration Number 0221U000216, 0120U105188 , R & D reports Title Chemical-genetic approach to the study of the effects of ACE-2 inhibition as a pharmacological model of COVID19 side effects in the nervous, intestinal, cardiovascular and hemostasis systems. popup.stage_title Head Riabukhin Serhii V., Доктор хімічних наук Registration Date 03-01-2021 Organization Taras Shevchenko National University of Kyiv popup.description2 Object of study: chemical compounds are potentially selective inhibitors of ACE2. Purpose: To synthesize 10 known selective ACE2 inhibitors on a scale of 1-10g. Using in silico screening of the world collection of screening compounds to identify new selective ACE2 inhibitors based on chemotypes that differ from known inhibitors. To develop a methodological approach for monitoring the kinetics of [14C] glycine transport in nerve terminals and permeability of intestinal epithelial cells (subcontractor - OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine). Research methods: organic synthesis, chemoinformatics analysis, in silico screening, molecular docking, molecular mechanics. Literature-known selective ACE2 inhibitors were analyzed. As a result, ten compounds with known inhibitory activity and selectivity were selected, covering all known chemotypes as widely as possible. Of the 10 selected compounds (each of which is obtained in ~ 10 synthetic stages) at the time of reporting synthesized 2, in grams, another 4 are at different stages of synthesis. During the performance of synthetic work, both known synthetic methods and new ones were optimized and scaled. A docking model was constructed to search for ACE2-selective inhibitors compared to ACE. In silico screening of the world collection of low molecular weight compounds by molecular dynamics and molecular docking methods was performed. Fifteen hit compounds were selected for further study. The project subcontractor developed a method for monitoring and obtaining experimental data on the uptake / release [14C] of glycine and [2,33H] aspartate in the nerve terminals of the brain. The methodology of registration of permeability of intestinal epithelial cells for amino acids is formulated.  Product Description popup.authors Avramenko Mykola М. Borysco Petro O. Volochnyuk Dmitriy M. Grabchuk Galyna P. Dovbynchuk Taisa V. Macedon Yelyzaveta S. Moroz Yurii S. Oxyuta Oleksandr V. Pashchenko Oleksandr Е. Subota Andrii I. Tolstanova Ganna M. popup.nrat_date 2021-01-03 Close