Activity of alkaloids from Alstonia macrophylla against Plasmodium falciparum
ฤทธิ์ต้านเชื้อมาลาเรีย Plasmodium falciparum ของแอลคาลอยด์จากต้นทุ้งฟ้า
(Alstonia macrophylla)
Niwat Keawpradub, Asst. Prof., D. of Pharmacognosy and Pharmaceutical Botany,
F. of Pharmaceutical Sci., PSU.
Steele, J. P., London School of Hygiene and Tropical Medicine, London, UK
Kirby, G. C., London School of Hygiene and Tropical Medicine, London, UK
Houghton, P. J., D. of Pharmacy, King's College London, UK
Corresponding e-mail : kniwat@ratree.psu.ac.th
Presented : The 4th NRCT-JSPS Joint Seminar in Pharmaceutical Sciences, "Drug Development through Biopharmaceutical Sciences, November 24-26, 1998, Hat Yai,
Songkhla
Key words : alkaloids, Alstonia macrophylla, Plasmodium falciparum
The methanol extract of the root bark of Alstonia macrophylla (Apocynaceae) showed interest-ing antiplasmodial activity against cultured multidrug-resistant K1 strain of Plasmodium falciparum with an IC50 value of 5.7 mg/ml. This activity was shown to reside in the alkaloidal fraction, from which three novel bisindole alkaloids, i.e. alstomacroline, alstomacrophylline and O-methylmacralstonine, were isolated along with ten known indole alkaloids. The chemical structures were determined by advanced spectroscopic methods, particularly 2D-NMR. The alkaloids were tested against the K1 strain of P. falciparum cultured in human erythrocytes. The growth of the parasites was measured for various concentrations (in 4-fold serial dilutions) of each alkaloid by determination of the reduction
in incorporation of [3H]-hypoxanthine into the parasites. From the values obtained the concentration of alkaloid reducing growth by 50% (IC50) was assessed. In general the monomeric indoles were considerably less active than the bisindoles with IC50 values greater than 5 mM. The bisindoles villalstonine and macrocarpamine exhibited pronounced antiplasmodial activity with IC50 values of 0.27 mM and 0.36 mM, respectively. The IC50 values of the three novel alkaloids were found in the
range of 0.65-1.60 mM. The mean IC50 value of chloroquine diphosphate, the positive control, tested in the same system was 0.20 mM. These results lend some support to the use of A. macrophylla in traditional medicine for the treatment of malaria.
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