Bryostatin discovery

Prominent amongst these marine discoveries are the bryostatins from the marine bryozoan Bugula neritincr, the dolastatins from the shell-less mollusc Dolabella auricularia the cephalostatins from the South African marine worm (a mere 5 mm long) Cephalodiscus gilchristi the sponge... 

The bryostatins represent one of the medically most promising series of marine animal constituents presently known. Their discovery, chemistry and biology will be reviewed here beginning with a historical perspective. 

Earlier, some of the same considerations had led me in 1957 to initiate a study of amphibian venoms of the steroidal bufadienolide (6) type as potential sources of new antineoplastic substances. Eventually we found that some of the toad venom bufadienolides such as marinobufagin significantly inhibit growth of the National Cancer Institute s KB cell line derived from a human nasopharynx carcinoma and lead to a curative response with the murine Ehrlich ascites system (7). However, the therapeutic indices were unattractive for further development. So the effort was extended in 1965-66, as Just noted, to encompass a geographically far-reaching area (Asia, Africa, Australia etc.) and an extensive research program to evaluate marine invertebrates and arthropods for structurally unique and useful anticancer constituents. Subsequently we isolated the first such invertebrate antineoplastic constituents (8-12). Meanwhile, our early expectations have been abundantly realized and the discovery of the bryostatins provides a splendid illustration. 

The initial discovery of bryostatin 3 (Figure 1.5, 38) was indirectly reported in 1970." Subsequent developments leading to the report of the isolation... 

Thus, just as in the case of the erythromycin basic structure, the synthesis and biological activities of macrocyclic compounds first reported almost 45 years ago, are still being investigated, with perhaps more interesting biological discoveries to come, particularly as it is now almost certain that bryostatins are produced by an as yet uncultured microbe found initially in the larvae of the bryozoan. Current information can be obtained by inspection of the review by the Haygood group published in 2010. ... 

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