Symposium “Plants in Health and Culture”
G. Philippe a, L. Angenot a, M. Frédérich a, L. Nguyenb, M. Tits a and J.M. Rigob
a Laboratory of Pharmacognosy, Natural and Synthetic Drugs Research Center, University of Liège, B36, Av. de l’Hôpital 1, 4000 Liège, Belgique
b Center for Cellular and Molecular Neurobiology, University of Liège, 4000 Liège, Belgique
Evaluation of strychnine-like properties of various alkaloids isolated from Strychnos icaja
Strychnos icaja Baill. (Loganiaceae) is a liana found in Central Africa which is known to be an arrow and ordeal poison but which is also used by traditional medicine to treat chronic malaria (1). Recently, many dimeric and trimeric indolomonoterpenic alkaloids with interesting antiplasmodial properties have been isolated from its root bark (2-4). As these alkaloids are derivatives of strychnine, it was important, in view of their potential use as antimalarial drugs, to check if they were devoid of convulsant strychnine-like properties. With this aim in view, their interaction with the strychnine-sensitive glycine receptor was investigated. The antagonistic effects of the antiplasmodial sungucine, strychnogucine B (dimerics) and strychnohexamine (trimeric) on glycine-gated currents in mouse spinal cord neurons in culture were measured by whole-cell patch clamp recordings. Protostrychnine, a monomeric alkaloid without antiplasmodial activity, also isolated from this Strychnos, and which differs from strychnine only by a cycle opening, was also studied in order to complete the structure-activity data.In comparison with strychnine, all compounds induced a weak to very weak inhibition of glycine-gated currents which did not seem to be dose-dependant. Another aspect of the interaction of these alkaloids with the glycine receptor is also studied by [3H]strychnine binding experiments on membranes from adult rat spinal cord. These assays are still in course of realization.
(1) Neuwinger, H. D. African Ethnobotany. Poisons and Drugs. Chemistry. Pharmacology. Toxicology., Chapman & Hall, London, 1996, 569-578.
(2) Frédérich, M., De Pauw, M.-C., Llabrès, G., Tits, M., Hayette, M.-P., Brandt, V., Penelle, J., De Mol, P., and Angenot, L., "New antimalarial and cytotoxic sungucine derivatives from Strychnos icaja roots", Planta Medica, 2000, 66, 262-269
(3) Frédérich, M., De Pauw, M.-C., Prosperi, C., Tits, M., Brandt, V., Penelle, J., Hayette, M.-P., De Mol, P., and Angenot, L., "Strychnogucines A and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja", Journal of Natural Products, 2001, 644
(4) Philippe, G., Prost, E., Nuzillard, J.-M., Zèches-Hanrot, M., Tits, M., Angenot, L., and Frédérich, M., "Strychnohexamine from Strychnos icaja, a naturally occuring trimeric indolomonoterpenic alkaloid", Tetrahedron Letters, 2002, 433, 3387-3390