Cytotoxic and antitumor potentialities of aporphinoid alkaloids.

Aporphinoids form an important group of plant secondary metabolites. Some of these compounds are used for a long time in traditional medicine for the treatment of various diseases, from benign syndromes to more severe illnesses. More than 500 aporphine alkaloids have been isolated from various plant families and many of these compounds display potent cytotoxic activities which may be exploited for the design of anticancer agents. Here we review the origin, biosynthesis, structure and cytotoxic properties of the prominent members of this class of compounds. Simple aporphinoids (boldine, dicentrine) as well as oxo-, pro- and dehydro-aporphines, and dimeric forms such as thalicarpine, are discussed here. Their mechanisms of action are not well known but DNA-manipulating enzymes such as polymerases and topoisomerases are among the most frequently cited targets for these benzylisoquinoline compounds. This review presents an updated view of the cytotoxic properties of the aporphinoids and their potential contribution to the development of anticancer agents.

Cytotoxic aporphine alkaloids from Cassytha filiformis.

Purification of a cytotoxic crude alkaloid extract of Cassytha filiformis led to the isolation of four known aporphine alkaloids: neolitsine, dicentrine, cassythine (= cassyfiline) and actinodaphnine. Their structures were determined by analysis of spectroscopic data. All isolated alkaloids were tested for their cytotoxic activities on cancer and non-cancer cell lines in vitro. Neolitsine was the most active against HeLa and 3T3 cells (IC 50 :21.6 microM, and 21.4 microM, respectively). Cassythine and actinodaphnine showed the highest activity against Mel-5 (IC 50 : 24.3 microM and 25.7 microM, respectively) and HL-60 (IC 50 : 19.9 microM and 15.4 microM, respectively). This is the first report on the cytotoxic activity of C. filiformis extract and of neolitsine and cassythine. Furthermore, the complete NMR data of cassythine and actinodaphnine are given here for the first time.

ent-trachyloban-3beta-ol, a new cytotoxic diterpene from Croton zambesicus.

The dichloromethane extract of leaves of Croton zambesicus (Euphorbiaceae) showing in vitro cytotoxicity against human cervix carcinoma cells was investigated in order to identify its active compounds. A bio-guided fractionation by HSCCC followed by MPLC led us to isolate a trachylobane diterpene, ent-trachyloban-3beta-ol, with cytotoxic properties (IC50 on HeLa cells = 7.3 microg/ml). This is the first report on the cytotoxicity of a trachylobane diterpene.