New Galantamine Derivatives with Inhibitory Effect on Acetylcholinesterase Activity

Abstract

Background: Inhibitors of acetylcholinesterase (AChE) are used to treat many disorders, among which are neurodegenerative upsets, like Alzheimer’s disease (AD). One of the limited licensed AChE inhibitors (AChEIs) used as drugs is the natural compound galantamine (Gal). Objective: As Gal is a toxic compound, here we expose data about its four derivatives in hybrid peptide-norgalantamine molecules, which have shown 100 times lower toxicity. Methods: Four newly synthesized galantamine derivatives have been involved in docking analysis made by Molegro Virtual Docker. Biological assessments were performed on ICR male mice. The change in short and long-term memory performance was evaluated by passive avoidance test. AChE activity and levels of main oxidative stress parameters: lipid peroxidation, total glutathione (GSH), enzyme activities of catalase (CAT), superoxide dismutase, and glutathione peroxidase were measured in brain homogenates. Results: Our experimental data revealed that the new hybrid molecules did not impair memory performance in healthy mice. Two of the compounds demonstrated better than Gal AChE inhibitory activity in the brain. None of them changed the level of lipid peroxidation products, one of the compounds increased GSH levels, and all of them increased CAT enzyme activity. Conclusion: The new galantamine-peptide hybrids demonstrated a potential for inhibition of AChE and antioxidant activity and deserve further attention.

Neuroprotective Effects of Myrtenal in an Experimental Model of Dementia Induced in Rats

“…As a muscarinic cholinergic receptor antagonist, Sc impairs brain cholinergic transmission (increasing AChE activity, reducing ACh levels, and inhibiting choline acetyltransferase activity). It increases brain oxidative stress levels and affects the memory processes, inducing cognitive deficits similar to those observed in AD patients [ 49 , 50 , 51 , 52 ].…”

Bioactive Compounds and Their Derivatives: An Insight into Prospective Phytotherapeutic Approach against Alzheimer’s Disease

“…Galantamine is an isoquinoline alkaloid found in the flowers and bulbs of Galanthus caucasicus , Galanthus sworonowii , and Leucojum aestivum , all of which are members of the Amaryllidaceae family [ 67 ]. Galantamine functions as an allosteric modulator of nicotinic acetylcholine receptors (nAChRs) [ 68 , 69 ].…”

Neuropsychopharmacological Induction of (Lucid) Dreams: A Narrative Review

“…Galantamine is a natural tertiary alkaloid from the Amarylidacea family, originally isolated from the bulbs of Snowdrop and Narcissus species [24] (Figure 2). In contrast to donepezil and rivastigmine, galantamine is not only an AChEI, but also a positive allosteric modulator of nicotinic ACh receptors.…”