Fonseca_2025_Pharmaceuticals.(Basel)_18_

Background/Objectives: Neurological and psychiatric disorders share overlapping mechanisms, such as oxidative stress, neuroinflammation, and neurotransmitter imbalance. In this context, multitarget natural molecules have gained attention. 1-nitro-2-phenylethane (1N2PE), a major constituent of Aniba canelilla essential oil, is known for its antioxidant, anti-inflammatory, and anticholinesterase effects, yet its neuropharmacological profile remains poorly understood. Methods: This study integrated in silico predictions and in vivo behavioral assays to characterize 1N2PE. Results: Pharmacokinetic analyses indicated favorable drug-like properties, with high gastrointestinal absorption, blood-brain barrier penetration, and no P-gp substrate profile. Molecular docking and dynamics revealed stable interactions with dopamine transporter (DAT, deltaG = -26.26 kcal/mol), prostaglandin-H synthase-1 (PGHS-1, deltaG = -20.27 kcal/mol), serotonin transporter (SERT, deltaG = -18.20 kcal/mol), and acetylcholinesterase (AChE, deltaG = -16.58 kcal/mol). In vivo, using a scopolamine-induced impairment model, 1N2PE significantly improved spatial memory and cognition in the Morris water maze. Treated animals reduced the distance to the target zone by ~40% compared with scopolamine-only rats (p < 0.01), normalized latency during training, and exhibited 30% less immobility (p < 0.05), indicating antidepressant-like effects. Moreover, 1N2PE attenuated anxiety-like thigmotaxis, restoring exploratory patterns (p < 0.0001). Conclusions: Together, these findings highlight 1N2PE as a multitarget candidate for cognitive and psychiatric disorders, combining favorable pharmacokinetic properties with preclinical efficacy, warranting further biochemical and translational investigations.