Synthesis, Molecular Docking, Druglikeness Analysis, and ADMET Prediction of the Chlorinated Ethanoanthracene Derivatives as Possible Antidepressant Agents

Abstract

Ethanoanthracene cycloadducts (5–7) anti, (5–7) syn, and (5–7) dec have been synthesized from the Diels–Alder (DA) reaction of diene 1,8-dichloroanthracene 2, with the dienophiles; acrylonitrile 3, 1-cynavinyl acetate 4, and phenyl vinyl sulfone 5, individually. The steric effect of dienophile substituents were more favorable toward the anti-isomer formation as deduced from 1H-NMR spectrum. The cheminformatics prediction for (5–7) anti and (5–7) syn was investigated. The in silico anticipated anti-depression activity of the (5–7) anti and (5–7) syn compounds were investigated and compared to maprotiline 9 as reference anti-depressant drug. The study showed that steric interactions play a crucial role in the binding affinity of these compounds to the representative models; 4xnx, 2QJU, and 3GWU. The pharmacokinetic and drug-like properties of (5–7) anti and (5–7) syn exhibited that these compounds could be represented as potential candidates for further development into antidepressant-like agents.