Natural stilbenes and analogues as antineoplastic agents

Natural compounds play a key role in the cancer prevention and treatment. Among them stilbene-based compounds are widely distributed in nature and show a wide range of biological activities. Certain poly-hydroxylated cis-stilbenes and their analogues bind in the colchicin site of tubulin and inhibit cancer cell proliferation. Up-to-now the most promising of these compounds is combretastatin A-4 (cis-3,4,4',5tetramethoxy-3'-hydroxy stilbene ) which has been shown to cause mitotic arrest in a variety of cancer cell lines, including multi-drug-resistant ones, and has also demonstrated cancer antiangiogenetic properties. The relative molecular simplicity of combretastatins, associated with their important anticancer properties, offers promises for the rational design of new chemotherapeutic agents. In this context, many efforts have been devoted to the detailed study of the structure-activity relationship of various substituted stilbenes as well as soluble prodrugs; to the development of new synthetic methods; and to the design of analogues with improved activities.