Biological Activities of Pyrrolidinoindoline Alkaloids from Calycodendron milnei

Abstract

Certain genera of the tribe Psychotrieae, specifically Calycodendron and Psychotria, found on Pacific Islands, synthesize a series of N _b-methyltryptamine-derived alkaloids made by linking together 2 to 8 pyrrolidinoindoline units. Nine alkaloids of this class have been isolated from the aerial parts and stem bark of Calycodendron milnei, a species endemic to the Vaté Islands (New Hebrides), and examined for potential application as anti-cancer and anti-infective agents. All members of the series exhibited readily detected cytotoxic activity against proliferating 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 antiviral activity against a DNA virus, herpes simplex type 1, and an RNA virus, vesicular stomatitis virus. All members of the series showed readily detected anti-bacterial, anti-fungal, and anti-candidal activities using both tube dilution and disc diffusion assay methods. The most potent anti-microbial alkaloids were hodgkinsine A and quadrigemine C, which exhibited minimum inhibitory concentration (MIC) values as low as 5 µg/ml.

Key words

Calycodendron milnei (A. Gray) A.C. Smith - Rubiaceae - pyrrolidinoindoline alkaloids - cytotoxicity - antiviral agent - anti-bacterial agent - anti-fungal agent - anti-candidal agent