1-Nitro-2-Phenylethane as a Multitarget Candidate for Cognitive and Psychiatric Disorders: Insights from In Silico and Behavioral Approaches.

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, ΔG = -26.26 kcal/mol), prostaglandin-H synthase-1 (PGHS-1, ΔG = -20.27 kcal/mol), serotonin transporter (SERT, ΔG = -18.20 kcal/mol), and acetylcholinesterase (AChE, ΔG = -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.