Cholinesterase inhibitors from fruits of Thai bitter gourd Momordica charantia L.

Abstract

Anti-acetylcholinesterase compounds were separated from the dichloromethane extract of Momordica charantia L. Four compounds and three inseparable mixtures were afforded and their chemical structures were elucidated on the basis of physical properties and spectroscopic analysis as well as comparing with the previous publication data. The isolated substances were (19R,23E)-5β,19-epoxy-19-methoxycucurbita-6,23,25-trien-3β-ol (1), (23E)-5β,19-epoxycucurbita-6,23-diene-3β,25-diol (2), a mixture of 5β,19-epoxycucurbita-6,23(E),25(26)-triene-3β,19(S)-diol (3a) and 5β,19-epoxycucurbita-6,23(E),25(26)-triene-3β,19(R)-diol (3b), a mixture of 5β,19-epoxy-25-methoxy-cucurbita-6,23-diene-3β,19(S)-diol (4a) and 5β,19-epoxy-25-methoxy-cucurbita-6,23-diene-3β,19(R)-diol (4b), ligballinol (5), a mixture of 3β-O-D-glucopyranosyl-24ξ-ethyl-cholesta-5-ene-3β-ol (6a) and 3β-O-D-glucopyranosyl-24β-ethyl-cholesta-5,25-diene-3β-ol (6b) or charantin and momordicoside K (7). Among them, 5β,19-epoxycucurbita-6,23(E),25(26)-triene-3β,19(S)-diol (3a) and 5β,19-epoxy-25-methoxy-cucurbita-6,23-diene-3β,19(S)-diol (4a) were first identified from nature. Moreover, ligballinol (5) was first isolated from this plant. Ligballinol (5) exhibited the most potent butyrylcholinesterase (BChE) inhibitory activity with the IC₅₀ value of 32.20 μM with a competitive mode of inhibition in a kinetic study.