Background:In vitro, the molecular docking method has been suggested for estimating
the biological affinity of the pharmacophores with physiologically active compounds. It is the latter
stage in molecular docking, and the docking scores are examined using the AutoDock 4.2 tool
program. The chosen compounds can be evaluated for in vitro activity based on the binding
scores, and the IC50 values can be computed.Objective:The purpose of this work was to create methyl isatin compounds as potential antidepressants,
compute physicochemical characteristics, and carry out docking analysis.Methods:The protein data bank of the RCSB (Research Collaboratory for Structural Bioinformatics)
was used to download the PDB structures of monoamine oxidase (PDB ID: 2BXR) and indoleamine
2,3-dioxygenase (PDB ID: 6E35). Based on the literature, methyl isatin derivatives
were chosen as the lead chemicals. By determining their IC50 values, the chosen compounds were
tested for in vitro anti-depressant activity.Results:The binding scores for the interactions of SDI 1 and SD 2 with indoleamine 2,3 dioxygenase
were found to be -10.55 kcal/mol and -11.08 kcal/mol, respectively, while the scores for
their interactions with monoamine oxidase were found to be -8.76 kcal/mol and -9.28 kcal/mol,
respectively, using AutoDock 4.2. The relationship between biological affinity and pharmacophore
electrical structure was examined using the docking technique. The chosen compounds were
tested for their ability to inhibit MAO, and the IC50 values for each were found to be 51.20 and
56, respectively.Conclusion:This investigation has identified many novel and effective MAO-A inhibitors from
the family of chemicals known as methyl isatin derivatives. Lead optimization was applied to the
SDI 1 and SDI 2 derivatives. The superior bioactivity, pharmacokinetic profile, BBB penetration,
pre-ADMET profiles, such as HIA (human intestinal absorption) and MDCK (Madin-Darby canine
kidney), plasma protein binding, toxicity assessment, and docking outcomes, have been obtained.
According to the study, synthesised isatin 1 and SDI 2 derivatives exhibited a stronger
MAO inhibitory activity and effective binding energy, which may help prevent stress-induced depression
and other neurodegenerative disorders caused by a monoamine imbalance.