# Neuroprotective Potential of New Monoterpene-Adamatane Conjugates—A Pilot Study

## TL;DR

This study explores new chemical compounds that may help protect the brain in diseases like Alzheimer's by improving memory and reducing stress.

## Contribution

The paper introduces novel monoterpene–aminoadamantane conjugates with multifunctional neuroprotective properties.

## Key findings

- MAC1, MAC3, and MAC4 showed strong predicted affinity for acetylcholinesterase and good blood–brain barrier permeability.
- The compounds improved memory deficits and oxidative stress markers in a rat model of dementia.
- Hybridization of myrtenal with aminoadamantane frameworks produced promising neuroprotective ligands.

## Abstract

Neurodegenerative diseases, including Alzheimer’s disease, are marked by cholinergic dysfunction, oxidative stress, and reduced neurotrophic support, which drives the quest for multifunctional therapeutic agents. This pilot study presents four novel monoterpene–aminoadamantane conjugates (MACs 1–4) designed to combine the antioxidant and neuromodulatory characteristics of monoterpenes with the neuroprotective properties of aminoadamantane derivatives. Their physicochemical characteristics, blood–brain barrier permeability, and binding affinity to human acetylcholinesterase (AChE) were evaluated using molecular docking and in silico descriptor analysis. In vivo, the neuroprotective efficacy of the MACs was investigated in a scopolamine-induced dementia model in rats, employing behavioral tests. Biochemical assays conducted in the hippocampus and prefrontal cortex assessed AChE activity, antioxidant enzyme performance, lipid peroxidation levels, total glutathione content, and BDNF concentrations. The findings indicate that MAC1, MAC3, and MAC4 demonstrate favorable calculated blood–brain barrier permeability, strong predicted affinity for AChE, and significant in vivo alleviation of scopolamine-induced memory deficits, in conjunction with improvement of key markers of oxidative stress and cholinergic function. These results show that the structural hybridization of myrtenal with aminoadamantane frameworks produces promising multifunctional ligands that are relevant for Alzheimer’s-type neurodegeneration.