The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated. Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum. Some of the stilbenes proved to be potent antimitotic agents which inhibited both tubulin polymerization and the binding of colchicine to tubulin. Combretastatin A-4 has been shown to be the most potent cancer cell growth inhibitor of the series. Presently this cis-stilbene is the most effective inhibitor of colchicine binding to tubulin and the simplest natural product yet described with such potent antitubulin effects. Combretastatin A-4, A-5, and A-6 were also found to inhibit growth of Neisseria gonorrhoeae. Details of the isolation and syntheses of combretastatins A-4 (2a), A-5 (2c), and A-6 (3a) have been described.
An investigation of the sea hare Dolabella auricularia from Papua New Guinea has led to discovery of the new cyclodepsipeptide dolastatin 16 (3) containing two new amino acid units designated dolamethylleuine (Dml) and dolaphenvaline (Dpv). The structural elucidation was achieved by means of high-field (500 MHz) NMR and tandem MS/MS mass spectral interpretations and allowed the assignment of cyclo-(Pro-Dpv-Pro-Dml-O-Lac-Pro-O-Hiv-MeVal). The new depsipeptide exhibited strong inhibition of growth against a variety of human cancer cell lines.
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