Docking, Synthesis, and In vitro Anti-depressant Activity of Certain Isatin Derivatives.

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.