Antineoplastic agents, 122. Constituents of combretum caffrum

An investigation of the South African tree Combretum caffrum (Com-bretaceae) for antineoplastic constituents was conducted by employing the astrocytoma bioassay (9 ASK). By this approach and a combination of solvent partition, steric exclusion, and adsorption chromatographic procedures, a substance designated combretastatin [la] was isolated and found to display significant (71-90% astrocyte reversal at 1–100μ-g/ml dose levels) astrocyte reversal and murine P-388 lymphocytic leukemia (PS) cell growth inhibition (ED₅₀0.011 μg/ml). The structure of (—)-combretastatin was elucidated by X-ray crystal structure analysis and confirmed by total synthesis. The absolute configuration at C-10 was assigned the R-configuration on the basis of Horeau esterification techniques. Other prominent, albeit PS- inactive, con-stitutents were found to be 3,3^;,4'-tri-0-methyleliagic acid [2] and acacetin [3].