Affiliations: [a] Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
| [b] Department of Organic Chemistry, University of Chemical Technology and Metallurgy, Sofia, Bulgaria
| [c] Institute of Molecular Biology, Bulgarian Academy of Science, Sofia, Bulgaria
Correspondence:
[*]
Correspondence to: Maria I. Lazarova, Institute of
Neurobiology, Bulgarian Academy of Sciences, Acad. Georgi Bonchev
Str., Block 23, Sofia 1113, Bulgaria. Tel.: +359 886317811;
E-mail: m.lazarova@gmail.com; Daniela S. Tsekova,
Department of Organic Chemistry, University of Chemical Technology
and Metallurgy, Kliment Ohridski 8, Sofia 1113, Bulgaria.
E-mail: d_tsekova@uctm.
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.
