New derivatives of galanthamine containing peptide fragments with β-secretase inhibitor
activity were synthesized. In position 6 of the galanthamine new shortened analogues of β-secretase
inhibitor OM 99-2 (Boc-Val-Asn-Leu-Ala-OH and Boc-Val-Asn-Leu-Ala-Val-OH) were included.
The new derivatives of the galanthamine in position 11 including Boc and norgalanthamine in P3 or P4 positions, Val in
P2’ position and benzylamin in P3’-position were also synthesized. All new peptides were investigated on mice for acute
toxicity. The test compounds were administered to mice via intraperitoneal (i.p.) route. They have low toxicity
(LD50>1000 mg/kg) after i.p. The compound 11-N-demethyl-11-N-N-[Boc-Asp(Asp-Leu-Ala-Val-NH-Bzl)]-Galanthamine
was investigated by two way active avoidance method. The compound has good influence on the conditioned reflexes,
which improved the processes of learning and memory. Inhibition activity of newly synthesized compounds was
monitored against BuChE and IC50 values are determined. All compounds show activity in micromolar concentration.
Compounds 5 and 6 have around 10 times higher activity than galanthamine. Compounds 4 and 9 also show good activity.
All newly synthesized compounds show low acute toxicity.
Keywords: Alzheimer’s disease, butyrylcholinesterase, galanthamine, norgalanthamine, peptides, training and memorizing studies.
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