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DOI: 10.1055/s-0030-1264743
Bioassay-guided isolation of antiplasmodial strychnos alkaloids from the stem bark of Strychnos icaja Baill.
Strychnos icaja Baill. is a 20–100m long liana distributed in all central Africa. The roots have been reported to be used by pygmies tribes in Cameroon to cure malaria [1]. Several alkaloids have been previously isolated from the roots, some of which, especially dimers have shown good in vitro antiplasmodial activities [2–6]. In the search of new antiplasmodial compounds from Strychnos species, the in vitro bioassay guided fractionation of the total alkaloid fraction of the stem bark using the chloroquine-sensitive 3D7 strain of Plasmodium falciparum was carried out and resulted in the isolation of two new tertiary alkaloids monomers, 15-hydroxyvomicine 1, 12-methoxyicajine 2 and a new dimer, Nb-oxyde sungucine 3 along with the known monomers, icajine 4, vomicine 5, 15-hydroxy-19,20a-epoxynovacine 6, 12-methoxy-19,20α-epoxyicajine 7, strychnine 8 and dimers sungucine 9, isosungucine 10, strychnogucine C 11 and bisnorhydroxytoxiferine 12. The compounds were isolated by a combination of silica gel chromatography columns, sephadex LH-20 and preparative TLC and their structures determined based on the analysis of their spectral data (UV, NMR and MS). The most active fractions were those containing dimers with IC50 ranging from 0.32 to 4.31µg/ml. The antiplasmodial activities of the known dimers were comparable to those previously reported against other strains of P. falciparum [3–6]. Compound 3 (IC50 3.4µg/ml) was about 3 times more active than sungucine 9 whereas the monomers 1 and 2 were inactive. Besides the new derivatives 1-3, compounds 4-7 and 9-12 are isolated for the first time from the stem bark.
Acknowledgements: This research was supported by the ‘Subside federal de la recherche' of the University of Liège, Belgium through a postdoctoral fellowship to A.T.T. and by the Belgian National Fund for Scientific Research (FNRS – grant N. 3.4533.10). M.F. is a research associate from the FNRS. The authors wish to thank Mr. J.-C. Van Heugen, ATC, Belgium for ESI-MS measurements.
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