Design and in
silico evaluation of oxadiazole linked chromone derivatives as anti-depressant agents
Gupta Dheeraj Rajesh, Murugeshwari Vidya, Kumar Pankaj and Kumar Abhishek
Res. J. Chem. Environ.; Vol. 28(1); 73-79;
doi: https://doi.org/10.25303/281rjce73079; (2024)
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.
