Antimalarial and cytotoxic activities of schizogane alkaloids isolated from Schizozygia coffaeoides

Schizozygia coffaeoides Baill. (Apocynaceae) is a monotypic shrub used in Kenyan folk medicine for treatment of skin diseases [1] and also as antimalarial (local ethnopharmacological investigations). Schizogane alkaloids represent a small group of hexacyclic N-acyl compounds that were first isolated from the roots of S. coffaeoides by Renner and co-workers [2, 3] but with doubts on the structure of two of the isolated compounds (isoschizogamine and isoschizogaline). Both structures were later revised [4, 5] and named isoschizoganes in which a five-membered (as in 2 and 3) rather than a six-membered (as in 1) lactam ring is present, thus revealing a hexacyclic skeleton of N-acyl tetrahydroquinoline type with an aminal moiety. We present here the in vitro antimalarial evaluation of crude CH₂Cl₂ extracts of roots and stems of S. coffaeoides that showed a more interesting activity for the stems (IC₅₀ 8.7µg/ml versus 17.3µg/ml for the roots) and then the bioassay guided fractionation of the stem CH₂Cl₂ extract that led to the alkaloid totum from which the iso- and schizoganes 1-3 were isolated. Unfortunately, they showed weak antiplasmodial activities (IC₅₀ 29, 28 and 24µg/ml for 1, 2 and 3 respectively), but in vitro cytotoxicity evaluation (MCF 7 cells) revealed interesting activities with IC₅₀ (µM) of 9.1, 2.9 and 7.9 for 1, 2 and 3 respectively (versus doxorubicin, IC₅₀ 0.5µM, as positive control). In conclusion, this study reveals the cytotoxic potential of this very restricted type of alkaloids.

References: 1. Omino, E. A. et a. (1993)J. Ethnopharmacol. 40: 167–180. 2. Renner U. (1964) Lloydia 27: 406–415. 3. Renner, U. et al. (1965) Helv. Chim. Acta 48: 308–317. 4. Hajicek, J. et al. (1998) Tetrahedron Lett. 39: 505–508. 5. Kariba, R. M. (2002)J. Nat. Prod. 65: 566–569.