Arizona State University

Arizona Board of Regents, a Body Corporate

Jun-Ping Xu

George R Pettit

Thomas H Smith

Delbert Herald

The present invention relates to the crystal structures of dolastatin 16, dolamethylleuine and dolaphenvaline. The present invention also relates to processes for preparing dolamethylleuine and dolaphenvaline. The present invention further relates to computer readable medium with crystal structural data and/or information stored thereon.

Crystal structures of dolastatin 16, dolamethylleuine and dolaphenvaline, and methods for preparing dolamethylleuine and dolaphenvaline

The Indo-Pacific marine sponge Ircinia ramosa has been found to contain two powerful (GI50 0.001 to &#x3c;0.0001 &#x3bc;g/ml) murine and human cancer cell growth inhibitors, denominated herein as irciniastatin A and irciniastatin B. Both were isolated (10-3 to 10-4% yields) by cancer cell line bioassay-guided techniques and named irciniastatins A (1) and B (2). Structural elucidation by a combination of spectral analyses, primarily high resolution mass and 2D-NMR (principally APT, HMQC, HMBC and ROESY) revealed unusual structures 1 and 2. 

Irciniastatins a and b

A human cancer cell line bioassay-directed investigation of the Western Pacific marine sponge agelas sp. led to isolation of a trace (7.42&times;10,% yield) cancer cell growth inhibitor (lung NCI-H460 GI,0.77 &mgr;g/ml to ovary OVCAR-3 GI,2.8 &mgr;g/ml) designated agelagalastatin. Agelagalastatin is the first example of a natural product containing a digalactofuranosyl unit.

Isolation and structural elucidation of the human cancer cell growth inhibitory compound denominated agelagalastatin

Cytostatic linear and cyclo-depsipeptides, &ldquo;Dolastatin 16&rdquo;, &ldquo;Dolastatin 18&rdquo;, and &ldquo;Dolastatin 17&rdquo;, are disclosed which are obtained from Indian Ocean shelless mollusk,. Methods of using the substances to inhibit malignant cell growth associated with neoplastic diseases in animals and humans are also disclosed, as well as pharmaceutical preparations containing Dolastatin 16, Dolastatin 17, and Dolastatin 18.

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Chandler, AZ, United States of America

Jun-Ping Xu