Arizona State University

Arizona Board of Regents, a Body Corporate

Rui Tan

George R Pettit

Robin K Pettit

Feng Gao

The present invention is directed to cyclodepsipeptide compounds having antineoplastic and/or antimicrobial activity, preferably Kitastatin 1. The present invention is further directed to methods of inhibiting cancer cell growth and/or microbial growth in a host inflicted therewith by administering cyclodepsipeptide compounds to the inflicted host.

Cyclodepsipeptides with antineoplastic activity and methods of using to inhibit cancer and microbial growth

Two new compounds which may be useful in the treatment of one or more neoplastic diseases through chemotherapy have been isolated from the Western Pacific Ocean marine sponge Phakellia sp. The cyclic octapeptides phakellistatin 10 and phakellistatin 11 are disclosed herein. As the included data demonstrate, phakellistatin 10 attained an LC.sub.50 of less than 10.sup.-5 M per milliliter against the MDA-MB-435 breast cancer cell line. It also achieved total growth inhibition for two breast cancers and two CNS cancer cell lines at a concentration of less than 10.sup.-6 M per milliliter. The included data for phakellistatin 11 shows a moderately higher level of in vitro activity as shown by an LC.sub.50 of less than 10.sup.-5 M per milliliter against the MDA-MB-435 breast cancer cell line and five other cell lines. It also achieved total growth inhibition for two breast cancers, one CNS cancer, one Ovarian cancer, and one non-small cell lung cancer cell lines at a concentration of less than 10.sup.-7 M per milliliter.

Isolation and structure of the human cancer cell growth inhibitory

An intensive long-term investigation of marine organisms as sources of new anticancer drugs has led to the isolation and structural elucidation (primarily by high field NMR and mass spectrometry) of halistatin 1, a new polyether macrolide of the halipyran-type, from the Western Indian Ocean sponge Phakellia carteri. Halistatin 1 (8.8.times.10.sup.-7 % yield) caused the accumulation of cells arrested in mitosis, inhibited tubulin polymerization, and inhibited the binding of radiolabeled vinblastine and GTP to tubulin.

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Mesa, AZ, United States of America

Rui Tan