FURTHER EXPERIMENTS ON STRUCTURE-ACTIVITY RELATIONSHIPS AMONG THE LYCORINE ALKALOIDS

Article abstract of DOI:10.1016/S0031-9422(00)83732-2

Key Word Index - Sternbergia lutea; Amaryllidaceae; ascorbate biosynthesis inhibition; phenanthridine alkaloids; lycorine; narciclasine; structure-activity relationships.Syhthetic lycorine analogues, five Amaryllidaceae alkaloids and narciclasine, all structurally related to lycorine, were tested for their ability to inhibit ascorbic acid biosynthesis in vivo.The highest potency observed was displayed by narciclasine followed by compounds having an aromatic C-ring.Derivatives modified at C-1 and/or C-2 were inactive, while the compound with a double bond between these positions is a weak inhibitor.Also lutessine and its deacetyl derivative having an α-methoxyl group bonded to C-4 of the D-ring appeared completely inactive.These results confirm that the presence of an appropriately substituted C-ring is a neccessary requirement for optimal 'responsetriggering' conctact between the lycorine derivatives and the specific receptor.Functional groups jutting out from the α-side of the molecule do not allow a good fit with the binding sites.