Interactive Properties of Alkaloids from Datura stramonium, Moringa oleifera, and Carica papaya with Human Receptor Proteins of Psychoactive Compounds from Cannabis sativa and Nicotiana tabacum

Datura stramonium, Moringa oleifera and Carica papaya are common plants in Nigeria that have been reported to possess some psychoactive effects. However, the interactions of their alkaloids with the molecular targets of common psychoactive compounds are not well established. This study assessed the interactive potentials of alkaloids from these plants with α4β2 nicotinic acetylcholine receptor (α4β2 nAChR) of nicotine from Nicotiana tabacum and the cannabinoid receptor 1 (CB1) of delta-9-tetrahydrocannabinol (THC) from Cannabis sativa. Protein structures were retrieved from Protein Data Bank while PubChem was used to obtain ligand structures. Molecular docking using UCSF Chimera determined the binding affinity of protein-ligand complexes, followed by molecular dynamics simulations to evaluate root mean square deviation and radius of gyration. ADMET analysis was performed using SwissADME and ProTox-II. Notably, apoatropine, hyoscyamine, and 3â,6â-ditigloyloxytropane from D. stramonium exhibited stronger α4β2 nAChR binding effects, compared to nicotine, and had CB1 binding affinities similar to THC. Among these high-affinity binding compounds, apoatropine maintained the most stable and compact structural conformation, relative to nicotine and THC. ADMET analysis indicated propitious physicochemical and drug-like properties for all plant-based alkaloids except N, α-L-rhamnopyranosyl vincosamide from M. oleifera and apoatropine, which were predicted to be carcinogenic. Additionally, over 50% of the plant-based alkaloids assessed are blood-brain barrier permeant, implying their propensity to mediate CNS effects. It is pertinent to regulate the use of these plants, particularly in tropical regions like Nigeria, where they are widely cultivated, consumed, and likely explored for recreational purposes based on their psychoactive effects.