THE LOCALISATIONS IN LIPOSOMAL MEMBRANES OF THE TETRAHYDROFURAN RING MOIETIES OF THE ANNONACEOUS ACETOGENINS, ANNONACIN AND SYLVATICIN, AS DETERMINED BY1H NMR SPECTROSCOPY

Abstract

The positions of the tetrahydrofuran (THF) ring moieties of annonacin (a mono-THF ring Annonaceous acetogenin) and sylvaticin (a non-adjacent bis-THF ring Annonaceous acetogenin) within liposomal membranes made of dimyristoylphosphatidylcholine (DMPC) were determined by proton (1H) nuclear magnetic resonance (NMR) spectroscopy. Based on1H intermolecular nuclear Overhauser effects (NOEs), the THF rings of both acetogenins studied reside near the polar interfacial head group region of the DMPC. Recently, we have reported that the THF rings of a series of asimicin type of Annonaceous acetogenins (with adjacent bis-THF rings) also reside near the interfacial head group of DMPC. We can now conclude that the Annonaceous acetogenins, containing either mono-, adjacent bis-, or non-adjacent bis-THF ring moieties, have their THF ring moieties at the interfacial region of membranes, i.e., the THF ring moiety seems to serve a role as an anchor in the lipid membranes. This may be related to the uniquely potent bioactivities that Annonaceous acetogenins exhibit at their enzyme-inhibitory sites within mitochondrial and plasma membranes.