Symplostatin 3 (1), a new analogue of dolastatin 10 (2), has been isolated from a tumor selective extract of a Hawaiian variety of the marine cyanobacterium Symploca sp. VP452. Compound 1 differs from 2 only in the C-terminal unit; the dolaphenine unit is substituted by a 3-phenyllactic acid residue. Symplostatin 3 (1) possesses IC(50) values for in vitro cytotoxicity toward human tumor cell lines ranging from 3.9 to 10.3 nM. It disrupts microtubules, but at a higher concentration than 2, correlating with the weaker in vitro cytotoxicity.
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