Antiangiogenic Alkaloids from Marine Organisms

Diaz-Marrero, Christopher A. Cray, Lianne McHardy, Kaoru Warabi, Michel Roberge, RaymondJ. Andersen 

The three main treatment modalities currently available to cancer patients are surgery, radiotherapy, and chemotherapy [1], Radiotherapy and chemotherapy non-selectively inhibit rapidly proliferating cells, including cancer cells, and the generality of the antiproliferative effect of these treatments leads to the severe dose-limiting toxicides experienced by cancer patients. In addition, the genetic instability of tumor cells facilitates the development of resistance to radiotherapy and cytotoxic chemotherapy that eventually causes these treatment approaches to fail in most patients with solid or metastatic tumors. 

Modem Alkaloids Structure, Isolation, Synth is and Biology. Edited by E. Fattorusso and O. Taglialatela-Scafati Copyright 2008 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31521-5 

Metastasis, the spread of cancer cells from a primary tumor to remote sites in the body, is frequently the ultimate cause of death from solid tumors. Current options for treatment or prevention of metastasis are very limited. Since vascularization of tumors (angiogenesis) provides conduits required for the spread of the tumor cells to other sites (metastasis), targeting tumor vasculature not only offers a noncytotoxic approach to eradicating primary solid tumors, it should also aid in preventing their spread via metastasis. 

3- Dimethylisoguanine (4) and its conjugate acid 1,3-dimethylisoguaninium (S) have been found in several marine organisms as summarized in Table 9.1. These purine alkaloids w ere first identified in the marine sponge Amphimedon viridis [6,7] and later in A. paraviridis [8]. Copp and cow orkers have also reported the isolation of 

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