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

Sigma receptors (σ(1) R and σ(2) 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 σ(2) activity. The σ(2) 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 σ(2) 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 σ(2) receptor efficacy. The purpose of this study was to evaluate the pharmacophoric features of different σ(2) 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 σ(2) 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 σ(1) and σ(2) receptors. Furthermore, MM/GBSA binding energy calculations were used to confirm the binding of ligands on the σ(2) over σ(1) receptor. These in silico findings will aid in the discovery of selective σ(2) ligands with good pharmacophoric properties and potency in the future.