Molecular docking, drug-likeness properties, and toxicity prediction of alkaloidal phytoconstituents of piper longum against monoamine oxidase enzyme-A as an anti-depressive agent

Depression is a multifaceted disorder characterized by dysregulation of the immune system, the hypothalamic–pituitary–adrenal (HPA) axis, neurotransmitter levels, and the neurotrophic system. Globally, it impacts approximately 280 million individuals. Although synthetic medications are commonly prescribed as the primary treatment, their use is frequently associated with a range of adverse side effects. To investigate the potential of alkaloidal phytoconstituents of Piper longum as an anti-depressive agent through a computational analysis. Molecular docking analysis, using AutoDock vina 1.2.0, was employed to assess binding energy and interaction of phytoconstituents against monoamine oxidase (MOA)-A. SwissADME server was used to predict pharmacokinetics and drug likeliness properties. Additionally, toxicity was predicted using StopTox and ProTox-II web server. Asarinine, Dehydropipernonaline, and Pipercide exhibited excellent binding affinities with ΔG of − 11.7 kcal/mol, − 11.2 kcal/mol, − 10.5 kcal/mol respectively. These phytoconstituents showed better affinity than the reference Moclobemide (ΔG = − 9 kcal/mol). The stability of the Asarinine-MOA-A complex was confirmed by MD simulation. Notably, Asarinine possessed favourable pharmacokinetic properties and drug likeliness properties. This study holds promise in the quest for potential antidepressant treatments, highlighting the strong binding affinity of Piper longum phytoconstituents against MOA-A.