The discovery and development of the combretastatins

The Combretaceae plant family (comprising 600 or more species) of shrubs and trees is divided among 20 genera, of which the Combretum genus (250 species) of tropical and deciduous trees encompasses the largest number. 1 Some 24 species of Combretum are well-known in African folk medicine for applications and problems ranging from heart and worm remedies to wound dressings, treatment for the mentally ill, and scorpion stings. 2 Only the Indian Combretum latifolium appears to have been recorded as a folk medical treatment for cancer. 3 However, over 30 years ago, as part of the U.S. National Cancer Institute’s (NCI’s) worldwide exploratory survey of terrestrial plants, both Combretum molle 4 and Combretum caffrum (Eckl. and Zeyh.) Kuntze were found to provide extracts significantly active against the murine P-388 lymphocytic leukemia (PS system). C. caffrum is a deciduous tree (growing to 15 m high) in Africa, found principally in the Eastern Cape and Transkei to Natal. This willow-like tree (“bushwillow”) is a common sight overhanging stream beds. In autumn, these trees become quite prominent, with displays of reddish-brown fruit and leaves that turn bright red before falling. 5 The powdered root bark has been used by the Zulu of South Africa as a charm to harm an enemy. 2