IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES

IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES

The aim of the work was to establish the spect­rum of biological activity of new derivatives of 9-bromo-1,2,3,4-tetrahydroacridine due to the limi­ted amount of literature data. In silico prediction of selected bromo-derivatives of hydrogenated acridines was performed using the SuperPred 3.0 web res...

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Date:2023
Main Authors: Farat, Oleg, Varenichenko, Svetlana, Markov, Victor, Yanova, Karolina
Format: Article
Language:English
Published: V.I.Vernadsky Institute of General and Inorganic Chemistry 2023
Online Access:https://ucj.org.ua/index.php/journal/article/view/557
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Journal Title:Ukrainian Chemistry Journal

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Ukrainian Chemistry Journal
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spelling oai:ojs2.1444248.nisspano.web.hosting-test.net:article-5572023-08-31T11:57:23Z IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES Farat, Oleg Varenichenko, Svetlana Markov, Victor Yanova, Karolina bromoderivatives of acridine, tac­rine, in silico prediction, DNA lyase, butyrylcholinesterase. The aim of the work was to establish the spect­rum of biological activity of new derivatives of 9-bromo-1,2,3,4-tetrahydroacridine due to the limi­ted amount of literature data. In silico prediction of selected bromo-derivatives of hydrogenated acridines was performed using the SuperPred 3.0 web resource. The obtained results were compared with the results of prediction of active drugs that contain the acridine cycle in their structure - Tacrine, Amiridine and Amsacrine. Results ≤80% were taken into account. The most promising compound was 9-bromo-1,2,3,4-tetra­hydro­acridine. A common predicted target for bro­mide-hydrogenated acridines and all three drugs is DNA-(apurine or apyrimidine site) lyase with binding probabilities ranging from 82-97.5%. Common predicted targets for 9-bromo-1,2,3,4-tetrahydroacridine derivatives, Tacrine and Amsacrine are butyrylcholinesterase (90.4-98.2%) and transcription factor 1-α (92.02-98.01 %). Cathepsin D, toll-like receptor 8 and glucose transporter are promising common targets for further research, but it should be noted that the probability of binding in these drugs was below 80%. All selected compounds were tested for Lipinski's criteria. In addition, in silico prediction of the acute toxicity of bromo-derivatives of acridine was performed in rats with four types of administration. The safest compound according to the oral method of administration is the compound 9-bromo-2-tert-butyl-1,2,3,4-tetrahyd­ro­ac­ridine (1570 mg/kg), while the compound 9-bromo-1,2 turned out to be more toxic than the others ,3,4-tetrahydroacridine (565.3 mg/kg). The estimated average lethal dose of Tacrine after a single oral dose to rats is 40 mg/kg. The prediction results confirmed the prospects of further research among the class of hydrogenated bromoderivatives of acridines. V.I.Vernadsky Institute of General and Inorganic Chemistry 2023-07-28 Article Article Organic chemistry Органическая xимия Органічна xімія application/pdf https://ucj.org.ua/index.php/journal/article/view/557 10.33609/2708-129X.89.06.2023.97-110 Ukrainian Chemistry Journal; Vol 89 No 6 (2023): Ukrainian Chemistry Journal; 97-110 Украинский химический журнал; Том 89 № 6 (2023): Ukrainian Chemistry Journal; 97-110 Український хімічний журнал; Том 89 № 6 (2023): Ukrainian Chemistry Journal; 97-110 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/557/287
institution Ukrainian Chemistry Journal
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datestamp_date 2023-08-31T11:57:23Z
collection OJS
language English
topic_facet bromoderivatives of acridine
tac­rine
in silico prediction
DNA lyase
butyrylcholinesterase.
format Article
author Farat, Oleg
Varenichenko, Svetlana
Markov, Victor
Yanova, Karolina
spellingShingle Farat, Oleg
Varenichenko, Svetlana
Markov, Victor
Yanova, Karolina
IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES
author_facet Farat, Oleg
Varenichenko, Svetlana
Markov, Victor
Yanova, Karolina
author_sort Farat, Oleg
title IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES
title_short IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES
title_full IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES
title_fullStr IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES
title_full_unstemmed IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES
title_sort in silico prediction of biological activity of bromo derivatives of hydroacridines
description The aim of the work was to establish the spect­rum of biological activity of new derivatives of 9-bromo-1,2,3,4-tetrahydroacridine due to the limi­ted amount of literature data. In silico prediction of selected bromo-derivatives of hydrogenated acridines was performed using the SuperPred 3.0 web resource. The obtained results were compared with the results of prediction of active drugs that contain the acridine cycle in their structure - Tacrine, Amiridine and Amsacrine. Results ≤80% were taken into account. The most promising compound was 9-bromo-1,2,3,4-tetra­hydro­acridine. A common predicted target for bro­mide-hydrogenated acridines and all three drugs is DNA-(apurine or apyrimidine site) lyase with binding probabilities ranging from 82-97.5%. Common predicted targets for 9-bromo-1,2,3,4-tetrahydroacridine derivatives, Tacrine and Amsacrine are butyrylcholinesterase (90.4-98.2%) and transcription factor 1-α (92.02-98.01 %). Cathepsin D, toll-like receptor 8 and glucose transporter are promising common targets for further research, but it should be noted that the probability of binding in these drugs was below 80%. All selected compounds were tested for Lipinski's criteria. In addition, in silico prediction of the acute toxicity of bromo-derivatives of acridine was performed in rats with four types of administration. The safest compound according to the oral method of administration is the compound 9-bromo-2-tert-butyl-1,2,3,4-tetrahyd­ro­ac­ridine (1570 mg/kg), while the compound 9-bromo-1,2 turned out to be more toxic than the others ,3,4-tetrahydroacridine (565.3 mg/kg). The estimated average lethal dose of Tacrine after a single oral dose to rats is 40 mg/kg. The prediction results confirmed the prospects of further research among the class of hydrogenated bromoderivatives of acridines.
publisher V.I.Vernadsky Institute of General and Inorganic Chemistry
publishDate 2023
url https://ucj.org.ua/index.php/journal/article/view/557
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first_indexed 2025-09-24T17:43:51Z
last_indexed 2025-09-24T17:43:51Z
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