24-Nor-allobetulins possess strong α-glucosidase inhibitory activity

Nat Prod Res. 2023 Nov-Dec;37(22):3806-3814. doi: 10.1080/14786419.2022.2154347. Epub 2022 Dec 14.

Abstract

A series of 24-nor-allobetulin derivatives holding 3β-hydroxy-, oxime, methoxyoxime, lactame and 4-bromobenzylidene substituents have been synthesized and their differences in the NMR spectra were studied in detail. It was revealed that 3-oxo-24-nor-allobetulin loses selectivity in the reaction of oximation and forms a mixture of Z/E oximes (and methoxyoximes) in contract to the related derivatives of native scaffold (that forms only E-isomers). The screening of α-glucosidase inhibitory activity revealed that 24-nor-allobetulins are more active than allobetulins. The lead 3-oxo-24-nor-allobetulin with IC50 0.49 µM was more than 60-fold and 500-fold active than acarbose and 3-oxo-allobetulin, respectively. We can conclude that the removal of the C-24 methyl group significantly increased the antidiabetic effect and 24-nor-allobetulins should be identified as the new and promising scaffolds as α-glucosidase inhibitors on the basis of triterpenoids.

Keywords: 24-nor-allobetulin; Triterpenoids; allobetulin; α-glucosidase inhibitory activity.