No abstract

We have shown that the planar formula of the polyindoline alkaloids (C, B, E and D) isolated from the leaves of Psychotria forsteriana agree respectively with Quadrigemine A, Quadrigemine B, Psychotridine, and Isopsychotndine C. Their cytotoxic activity on cultured rat hepatoma cells (HTC line) is reported in this paper. These alkaloids showed a higher toxicity on HTC cells than vincristine, a bisindole alkaloid currently used in antitumor chemotherapy.

The genus Psychotria is widely spread in all the tropical underwoods. Previous studies of two species growing in Pacific Islands have shown alkaloids of polyindolinic structure e.g. Psychotridine (C25H62N10) in Psychotria beccaroides Wernh. (New Guinea) (1) and Hodgkinsine (C331-138N6), Quadrigemine (C and D) (CH50N8), Isopsychotridine (A and B) and Psychotridine (C25H62N10) in Psychotria oleoides (Baill.) Schlecht. (2). All these alkaloids result from the condensation of three, four, or five pyrrolidinoindolin units (Fig. 1: Isopsychotridine A, B. or C). Psychotria fcirsteriana A. Gray is a species growing in Vanuatu (New Hebrides). The alkaloidal content of the leaves were extracted with alkaline ethanol, and then purified by organic solvents and by chromatography on alumina. The final separation was obtained through semi-preparative HPLC.

Quadrigemine B, quadrigemine A, isopsychotridine C and psychotridine, isolated from PSYCHOTRIA FORSTERIANA, are potent inhibitors of the aggregation of washed human platelets induced by ADP, collagen or thrombin. The four compounds are active in the 1-10 microM range. The quadrigemine-type alkaloids do not increase the level of platelet cyclic AMP, either alone or in the presence of 20 nM prostaglandin E, (PGE (1)), an activator of adenylate cyclase. The characteristics of the pharmacological action of these compounds suggest that they act at a later stage in platelet activation, possibly through an interaction with cytoskeletal proteins.

Table 2 Inhibitory activity (%) Son 5-LO. Concentration Compound (50 tiM) Cardanolfraction 41.4