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

1 ABSTRACT Víchová Barbora: Biological activity of Peganum harmala L. alkaloids and their semi-synthetic derivatives I. Diploma thesis 2022. Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany β-Carboline alkaloids are natural substances with potential use in tumor therapy. In particular harmine, which acts cytotoxically by several mechanisms. The aim of the diploma thesis was to prepare N9-derivatives of harmine derivatives, to clarify their structure based on common spectrometric and spectroscopic methods (ESI, ESI-MS, NMR) and subsequently to study their biological activity (cytotoxicity, AChE, BchE and GSk-3beta inhibition). These tests resulted in several active derivatives, suitable candidates for further study. 9-N-(2-nitrobenzyl)harmine (HMA-22) was significantly cytotoxic to the Jurkat cell line (16% cell viability after 48 hours, compared to the control, with better cytotoxicity than the standard doxorubicin at a concentration of 1 μM). Another very active derivative was found 9-N-(5-bromopentyl)harmine (HMA-30), which was more cytotoxic to most tested cell lines than doxorubicin (1 μM), similarly as most of other derivatives. HMA-30 was also found as a potent BChE inhibitor (IC 50 4.06 ± 0.48 μM). 9-N-(4-nitrobenzyl)harmine (HMA-20)..