BIOLOGICAL-ACTIVITIES OF PYRROLIDINOINDOLINE ALKALOIDS FROM CALYCODENDRON MILNEI

Certain genera of the tribe Psychotrieae, specifically Calycodendron a nd Psychotria, found on Pacific Islands, synthesize a series of N-h-me thyltryptamine-derived alkaloids made by linking together 2 to 8 pyrro lidinoindoline units. Nine alkaloids of this class have been isolated from the aerial parts and stem bark of Calycodendron milnei, a species endemic to the Vate Islands (New Hebrides), and examined for potentia l application as anti-cancer and anti-infective agents. All members of the series exhibited readily detected cytotoxic activity against prol iferating and non-proliferating Vero African green monkey kidney cells in culture, with the most potent activity being exhibited by vatamine and quadrigemine C. Only hodgkinsine A exhibited substantial antivira l activity against a DNA virus, herpes simplex type 1, and an RNA viru s, vesicular stomatitis virus. All members of the series showed readil y detected anti-bacterial, anti-fungal, and anti-candidal activities u sing both tube dilution and disc diffusion assay methods. The most pot ent anti-microbial alkaloids were hodgkinsine A and quadrigemine C, wh ich exhibited minimum inhibitory concentration (MIG) values as low as 5 mu g/ml.