Terpenoid Anti-Cancer Agents

Only small doses of Vinblastine and Vincristine are tolerated and both alkaloids induce bone marrow depression and leucopaenia [429-432] which is reversible on discontinuation of therapy. In addition to causing a reversible 

Since anti-malignant properties in the Vinca rosea alkaloids are apparently confined solely to certain of the dimeric indole compounds, there being no 

It remains to be seen, however, whether these latter compounds or structural modifications of them will find application chnically. Certainly any earher hopes for useful therapeutic application of the triterpenoid cucurbitacins as founded on the high order of their cytotoxicity in vitro [479-484] have been dashed on account of the very low margins between the active and the toxic doses as revealed in in vivo experiments. Since the earlier review was written the structures of the cucurbitacins have been elucidated in full and they have been found to represent an unusual structural type in which backbone rearrangement in the formal carbonium ion initially formed from the cychsation of squalene epoxide in chair-boat-chair-boat conformational sequence proceeds beyond the stages giving rise to lanosterol and cycloartenol. Thus they can be regarded as overshoots of the biosynthetic pathway giving rise to the steroids in the same way as fusidic acid (LX), cephalosporin and helvolic acid represent undershoots of the same pathway. The structure of cucurbitacin A is as depicted in LXIV [485, 486]. 

Similarly, high toxicity mihtates against any useful therapeutic application of the anti-tumour properties [45, 487] of the unusually constituted sesquiter-penoid, illudin S (LXV) [47] (syn. lampterol [46]), just as the marked activity against Staphylococcus aureus [488] displayed by marasmic acid (LXVI) [489, 

which is considered [491, 492] to arise by an alternative pathway from a biogenetic intermediate held in common with illudin S, would seem to have no future in clinical medicine. Again, the high in vitro cytostatic activity shown by the verrucarins A and B and by roridin A [493] would seem to have little 

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