Selectivity profile comparison for certain γ-butyrolactone and oxazolidinone-based ligands on a sigma 2 receptor over sigma 1: a molecular docking approach

Abstract

Sigma receptors (σ₁ R and σ₂ R) are pharmacologically characterized membrane-bound receptors that bind a wide range of chemical compounds. Alzheimer's disease, traumatic brain injury, schizophrenia, and neuropathic pain have all been associated with abnormal σ₂ activity. The σ₂ receptor has recently been identified as a potential therapeutic target for inhibiting the formation of amyloid plaques. Numerous laboratories are now investigating the potential of σ₂ ligands. Small molecule discovery is the focus of current research, with the goal of using target-based action to treat a variety of illnesses and ailments. Functionalized γ-butyrolactone and oxazolidinone-based ligands, in particular, are pharmacologically important scaffolds in drug discovery research and have been thoroughly examined for σ₂ receptor efficacy. The purpose of this study was to evaluate the pharmacophoric features of different σ₂ receptor ligands using in silico techniques. This study used a library of 58 compounds having a γ-butyrolactone and oxazolidinone core. To investigate the binding characteristics of the ligands with the σ₂ receptor, a 3D homology model was developed. To understand the binding pattern of the γ-butyrolactone and oxazolidinone based ligands, molecular docking studies were performed on both σ₁ and σ₂ receptors. Furthermore, MM/GBSA binding energy calculations were used to confirm the binding of ligands on the σ₂ over σ₁ receptor. These in silico findings will aid in the discovery of selective σ₂ ligands with good pharmacophoric properties and potency in the future.