Tryptamine Derivatives of Sesquiterpene Lactones as Effective β-Secretase 1 Inhibitors

Modification of eudesmane-type sesquiterpene lactones and their epoxy derivatives with tryptamines was carried out using the aza-Michael reaction. A series of conjugates was obtained and their inhibitory properties were assessed against the β-secretase activity, which limits the rate of β-amyloid peptide formation and is a promising target for the treatment of Alzheimer’s disease. It was found that compounds containing a 5-methoxytryptamine moiety show the greatest activity, reducing protease activity by 65–95% at a concentration of 100 µM and with an IC 50 in the range from 15 to 48 µM. This allows us to consider the studied compounds as potential therapeutic agents against Alzheimer’s disease.