Antidepressant-like Activities of Boldine Analogues Combined with in Silico Computational Studies

Abstract

ABSTRACT: In order to investigate the potential antidepressant activity of Boldine (BO), five derivatives were synthesized whose structures were confirmed by 1H-NMR and 13C-NMR. MTT assay was employed to evaluate the neuroprotective properties of BO and derivatives on PC12 cells induced by corticosterone (CORT). And potential antidepressant activities of compounds were evaluated by in vivo experiments. Furthermore, ADME/T profiles were predicted by an in silico study. Binding poses of BO and BO-1 with putative macromolecular targets were predicted by molecular docking. Using molecular dynamics simulation is invaluable in gaining a better insight about the dynamical interaction behaviour of this virtual complex, ultimately, supporting or refuting the conclusion that 5-HTRs are the putative target for the hit compounds. The results showed that BO and its derivatives possess certain neuroprotective effect and the BO-1 was screened as a hit compound and its antidepressant activity was concluded by performed the TST test. Furthermore, 5-HTRs were identified as the potential targets of action by computational studies. This work provides ideas for extending pharmacological use of BO and the development of antidepressant agents.