Biological activity evaluation of substances of natural origin I.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical botany Candidate: Júlia Kupčíková Supervisor: PharmDr. Daniela Suchánková, Ph.D. Title of diploma thesis: Biological activity evaluation of substances of natural origin I. Alzheimer's disease (AD) is progressive neurodegenerative brain disorder characterized by memory loss and cognitive impairments. Manifestation of this disease is associated with decreased level of acetylcholine. Current treatment of AD is symptomatic and involves mainly restoring of acetylcholine levels through cholinesterase inhibition. Galanthamine, one of acetylcholinesterase inhibitors indicated for the treatment of AD belongs to Amaryllidaceae alkaloids. Therefore, other Amaryllidaceae alkaloids and their derivatives are prepared and studied for similar inhibitory properties. Amaryllidaceae alkaloid vittatine does not have cholinesterase inhibitory properties, but previous findings proved that some vittatine derivatives have potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Seven new semisynthetic derivatives of vittatine were prepared and studied for their inhibitory potential against both cholinesterases, using the Ellman's method. Significant BuChE inhibitory activity was..