Design and in silico evaluation of oxadiazole linked chromone derivatives as anti-depressant agents

Abstract

Depression is a common CNS disorder due to disturbances in the serotonin and dopamine level within the brain. In this study, different derivatives (C1-C32) of oxadiazole-linked chromone were designed and in silico studies were performed to investigate its anti-depressant activities. Compounds were docked with 5HT1 receptors to do so and MMGBSA and ADMET properties were evaluated. Further, compounds pharmacophore modeling and antidepressant activity were calculated using the phase and PASS tools. Among 32 designed compounds, C15, C29 and C31 showed the highest docking scores of -7.617, -7.269 and -7.325 kcal/mol and exhibited significant interaction with 5HT1 receptors compared to the standard drug imipramine. Compound C15 showed the highest binding efficiency with a binding energy of -77.79; the expected common is having a binding energy of -47.20. ADME properties show that all the designed compounds followed the rule of five. Further ligand-receptor complex potential interactions were evaluated using pharmacophore modeling, indicating that the compound has steric and electronic features to ensure the interaction with the selected receptor. Further, the antidepressant activity was predicted. Compounds C15 and C21 have the highest possibility of being antidepressant molecules with 0.827 and 0.833 pa values.