(2-Cyclohexyl-1-methylpropyl) cyclohexane isolated from garlic extract exhibits antidepressant-like activity: extraction, docking, drug-like properties, molecular dynamics simulations and MM/GBSA studies

Depressive disorders are among most common psychiatric diseases and second most common form of psychiatric illness globally. Commonly available chemical drugs used for treatment of nervous system disorders exert undesirable effects. Therefore, there is a growing need towards exploring novel antidepressants of herbal origin. Earlier, the antidepressant effect of methanolic extract of garlic has been shown. In this study, the ethanolic extract of garlic was prepared and chemically analysed using Gas Chromatography - Mass Spectrometry (GC-MS) screening. A total of 35 compounds were found to be present, which might act as antidepressant. Using computational analyses, these compounds were screened as potential inhibitors (selective serotonin reuptake inhibitor (SSRI)) against serotonin transporter (SERT)/leucine receptor (LEUT). In silico docking studies and other physicochemical, bioactivity and ADMET studies resulted in the selection of compound 1 ((2-Cyclohexyl-1-methylpropyl) cyclohexane) as potential SSRI (binding energy -8.1 kcal/mol) compared to known reference SSRI fluoxetine (binding energy -8.0 kcal/mol). Analysis of conformational stability, residue flexibility, compactness, binding interactions, solvent accessible surface area (SASA), dynamic correlation, and binding free energy predicted from molecular mechanics (MD) with generalised Born and surface area solvation (MM/GBSA) studies revealed formation of a more stable SSRI like complex with compound 1 having strong inhibitory interaction compared to known SSRI fluoxetine/reference complex. Thus, compound 1 may act as an active SSRI leading to discovery of potential antidepressant drug.Communicated by Ramaswamy H. Sarma