Molecular Interaction Profiling of Cathinone Derivative via Docking and Computational Tools

ABSTRACT The abusive use of new psychoactive substances (NPS), cathinones as a alternatives to traditional drugs, is a persistent issue that poses a major risk to public health. Cathinone derivatives influence the release and absorption of neurotransmitters of several biogenic amines, norepinephrine (NE), dopamine (DA), and serotonin (5‐HT or SER), which play a key role in regulating mood, perception, and behavior in the nervous system. However, these effects are accompanied by significant risks, including psychosis, cardiovascular issues, and other severe health complications, making synthetic cathinones a dangerous class of substances. The market is flooded with such synthetic drugs, but there are not many details regarding these designer drugs' mode of action, are available, which results in challenges for their prevention and treatment. Computational and theoretical research, such as dynamics simulations, molecular docking, and structure–activity relationship (SAR) assessments, offers invaluable insights into these interactions at the atomic level. In the present work, we have provided combined density functional theory and molecular docking to understand the mechanism of action of newly synthesized Cathinone derivative 1(4 methylphenyl)2 (ethylamino)pentan1one (4‐MEAP). MEP, HOMO–LUMO, NBO, and Hirshfeld surface analysis are presented for the title molecule. Docking analyses of 4‐MEAP with Dopamine (6M0Z), Norepinephrine (6M0F), and Serotonin (6M2R) transporters revealed that 4‐MEAP could favorably interact with 6M0Z, 6M0F, and 6M2R, which supports the molecule's potential as a therapeutic agent as well as a substance of concern due to its potential for abuse and psychoactive effects.