Cytotoxic and tubulin-interactive hemiasterlins from Auletta sp and Siphonochalina spp. sponges

Chemical and biological investigations of extracts from the sponge genus Au letta and two collections of Siphonochalina sp. have shown these organisms to be producers of the potent hemiasterlin class of antitumor agents. In ad dition to the previously known hemiasterlin (1) and hemiasterlin A (2), a n ew analogue, hemiasterlin C (3), was isolated and identified. The structure s of 1 and 2 were assigned based on comparison to literature values, and 3 was identified on the basis of H-1 NMR, C-13 NMR, COSY, HSQC, and HMBC expe riments. The cytotoxic and antitubulin activities of 1-3 were evaluated. In a comparative assay for inhibition of tubulin polymerization, the hemiaste rlins were more potent than dolastatin 15 and equipotent with cryptophycin 1, but were somewhat less potent than dolastatin 10. (C) 1999 Published by Elsevier Science Ltd. Printed in Great Britain.