3D-ALMOND-QSAR Models to Predict the Antidepressant Effect of Some Natural Compounds

Abstract

The current treatment of depression involves antidepressant synthetic drugs that have a variety of side effects. In searching for alternatives, natural compounds could represent a solution, as many studies reported that such compounds modulate the nervous system and exhibit antidepressant effects. We used bioinformatics methods to predict the antidepressant effect of ten natural compounds with neuroleptic activity, reported in the literature. For all compounds we computed their drug-likeness, absorption, distribution, metabolism, excretion (ADME), and toxicity profiles. Their antidepressant and neuroleptic activities were predicted by 3D-ALMOND-QSAR models built by considering three important targets, namely serotonin transporter (SERT), 5-hydroxytryptamine receptor 1A (5-HT1A), and dopamine D2 receptor. For our QSAR models we have used the following molecular descriptors: hydrophobicity, electrostatic, and hydrogen bond donor/acceptor. Our results showed that all compounds present drug-likeness features as well as promising ADME features and no toxicity. Most compounds appear to modulate SERT, and fewer appear as ligands for 5-HT1A and D2 receptors. From our prediction, linalyl acetate appears as the only ligand for all three targets, neryl acetate appears as a ligand for SERT and D2 receptors, while 1,8-cineole appears as a ligand for 5-HT1A and D2 receptors.

Study on the opening effect of eucalyptol on the blood–brain barrier and its brain pharmacokinetics

“…Recent studies have shown that eucalyptol regulates the neurotransmitters in the brain. It is a compound that restores 5‐HT exocytosis (Kim et al, 2022), and molecular docking studies have shown that it can bind to both dopamine receptors D 2 and 5‐HT1A (Avram et al, 2021). Moreover, it uses the GABA (γ‐aminobutyric acid)/benzodiazepine receptor to mediate the anxiolytic effects (Dougnon & Ito, 2020).…”

“…Recent studies have shown that eucalyptol regulates the neurotransmitters in the brain. It is a compound that restores 5-HT exocytosis (Kim et al, 2022), and molecular docking studies have shown that it can bind to both dopamine receptors D 2 and 5-HT1A (Avram et al, 2021).…”

Bioinformatics Tools for the Analysis of Active Compounds Identified in Ranunculaceae Species

“…Studies in the literature describe the usefulness of polyphenols and some alkaloids in the central nervous system, having a beneficial effect in a series of diseases from anxiety, depression, Alzheimer’s disease, and Parkinson’s disease. Studies suggest the neuroprotective effect of the compounds by reducing inflammation in the brain and by neutralizing oxidases [ 18 , 28 , 29 , 30 , 34 , 73 , 74 ].…”

“…The chemical structure of the compounds influences their pharmacological activity [ 80 ]. The three-dimensional arrangement of the atoms in the molecule can play an important role in the activity of the compounds both in the accessibility to the active sites and for the interaction of the drug with the targeted receptor [ 18 ]. The polar molecular surface shows the effective space occupied by the atoms of the molecule [ 81 ].…”

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity

“…Quantitative structure–activity relationships (QSAR) investigations are a fast computational approach for predicting a compound’s biological activity from its chemical structure. QSAR techniques aid medicinal chemists in comprehending the link between hypoglycaemic action and molecular characteristics [ 110 , 111 , 112 ]. Statistical measures such as the cross-validated correlation coefficient, fitted correlation coefficient, and standard deviation of error prediction are commonly used to assess QSAR investigations [ 113 ].…”