Biological activity of Peganum harmala L. alkaloids and their semi-synthetic derivatives II.

Fejtková Martina: Biological activity of Peganum harmala L. alkaloids and their semi-synthetic derivatives II. Diploma thesis 2022. Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy und Pharmaceutical botany. This diploma thesis deals with the preparation of semi-synthetic derivatives of the alkaloid harmine and the study of their biological activity. The alkaloid harmine was isolated by preparative TLC from an alkaloid extract, exactly from its subfraction PH-F1. Semi-synthetic derivatives were prepared by incorporation of different substituents in the N9 position of harmine. For the purposes of this diploma thesis were prepared 17 derivatives, which were subsequently identified on the basis of LC-MS, ESI-HRMS and NMR analysis. After structural elucidation of prepared derivatives, their biological activity was studied. The prepared substances were tested for their inhibitory effect on human acetylcholinesterase (AChE), human butyrylcholinesterase (BuChE), glykogen synthase kinase 3β (GSK-3β) and their cytotoxic activity was also measured on selected tumor and leukemia lines and one healthy cell line. Some of the prepared derivatives showed interesting selective inhibitory potencial against human BuChE, the most active derivative was..