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

Area of Science:

• Medicinal Chemistry
• Neuroscience
• Pharmacology

Background:

• Neurodegenerative diseases like Alzheimer's are characterized by cholinergic dysfunction, oxidative stress, and reduced neurotrophic support.
• There is a need for multifunctional therapeutic agents to address these complex pathological hallmarks.

Purpose of the Study:

• To design and synthesize novel monoterpene-aminoadamantane conjugates (MACs) combining antioxidant and neuroprotective properties.
• To evaluate the physicochemical characteristics, blood-brain barrier (BBB) permeability, and acetylcholinesterase (AChE) binding affinity of these novel compounds.
• To assess the in vivo neuroprotective efficacy and impact on oxidative stress and cholinergic function in a scopolamine-induced dementia model.

Main Methods:

• In silico analysis including molecular docking and descriptor analysis for physicochemical properties and BBB permeability.
• In vivo assessment using a scopolamine-induced dementia rat model with behavioral tests.
• Biochemical assays in hippocampus and prefrontal cortex to measure AChE activity, antioxidant enzymes, lipid peroxidation, glutathione, and BDNF levels.

Main Results:

• MAC1, MAC3, and MAC4 exhibited favorable calculated BBB permeability and strong predicted affinity for AChE.
• These compounds significantly alleviated scopolamine-induced memory deficits in rats.
• Treatment improved key markers of oxidative stress and restored cholinergic function.

Conclusions:

• Structural hybridization of myrtenal with aminoadamantane frameworks yields promising multifunctional ligands.
• These novel MACs are relevant for therapeutic strategies targeting Alzheimer's-type neurodegeneration.
• The study highlights the potential of these conjugates in addressing multiple pathological aspects of neurodegeneration.