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

Mohyeddine Al-Qubati,Mansour S. A. Galil,Assem Barakat,Mujeeb A. Sultan,Mufeed M. Omar

doi:10.3390/app10217727

Mohyeddine Al-Qubati, Mansour S. A. Galil + Show 3 more

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https://doi.org/10.3390/app10217727

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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.

Highlights

Anthracenes are known scaffold due to their versatile applications, including pharmaceutical drugs [1,2,3,4,5,6,7,8,9] and molecular sensors [10]
Building an ethano-bridge on the central ring of anthracenes is an attractive approach, and ethanoanthracenes are of significant interest in the context of drug discovery of anticancer [5,6], antimalarial [15,16], and antidepressant agents, as well as in overcoming drug resistance in multi-drug resistant cancers [17,18,19]
(1 mL) xylene was added into a 10 mL microwave reaction tube containing a stir bar

Summary

Introduction

Anthracenes are known scaffold due to their versatile applications, including pharmaceutical drugs [1,2,3,4,5,6,7,8,9] and molecular sensors [10]. Anthracenes, as a core structure, are explored in many transformations, due to more electrons, with the largest coefficients at C9/C10 [11,12,13,14]. Building an ethano-bridge on the central ring of anthracenes is an attractive approach, and ethanoanthracenes are of significant interest in the context of drug discovery of anticancer [5,6], antimalarial [15,16], and antidepressant agents, as well as in overcoming drug resistance in multi-drug resistant cancers [17,18,19]. Nobel Prize in chemistry in 1950, is one of the most useful synthetic approaches for building ethanoanthracenes [21,22,23].

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