IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES

Abstract

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.