1: Planta Med.  2004 May;70(5):407-13.  

Alkaloids from Cassytha filiformis and related aporphines: antitrypanosomal
activity, cytotoxicity, and interaction with DNA and topoisomerases.

Hoet S, Stevigny C, Block S, Opperdoes F, Colson P, Baldeyrou B, Lansiaux A,
Bailly C, Quetin-Leclercq J.

Laboratoire de Pharmacognosie, Unite d'Analyse Chimique et Physico-Chimique des
Medicaments, Universite Catholique de Louvain, Bruxelles, Belgium.

Cassytha filiformis (Lauraceae), a widely distributed parasitic plant, contains
several aporphine alkaloids and is often used in African folk medicine to treat
cancer, African trypanosomiasis and other diseases. In a previous investigation,
we showed that the alkaloid plant extract and the isolated aporphines possessed
in vitro cytotoxic properties. In this paper, we evaluated the in vitro activity
of the alkaloid extract (IC50 = 2.2 microg/mL) and its three major aporphine
alkaloids (actinodaphnine, cassythine, and dicentrine) on Trypanosoma brucei
brucei as well as four related commercially available aporphines (bulbocapnine,
glaucine, isocorydine, boldine). Only the three alkaloids from Cassytha
filiformis were active on the trypanosomes in vitro (IC50 = 3-15 microM).
Additionally, we compared the cytotoxicity of these seven compounds on HeLa
cells. Glaucine was the most cytotoxic compound on HeLa cells (IC50 = 8.2
microM) in the series. In order to elucidate their mechanism of action, the
binding mode of these molecules to DNA was studied by UV absorption, circular
and linear dichroism spectroscopy. The results of the optical measurements
indicated that all seven aporphines effectively bind to DNA and behave as
typical intercalating agents. Biochemical experiments showed that
actinodaphnine, cassythine and dicentrine also interfere with the catalytic
activity of topoisomerases in contrast to the four other aporphines. These
interactions with DNA may explain, at least in part, the effects observed on
cancer cells and on trypanosomes.

PMID: 15124084 [PubMed - in process]