Antineoplastic agents 370. Isolation and structure of dolastatin 18

Bioassay-guided separation of cancer cell growth inhibitory fractions derived from the sea hare Dolabella auricularia obtained in Papua New Guinea led to isolation (1.51 × 10−7% yield) of the new thiazole-containing peptide, dolastatin 18 (4). Structural determination was completed by employmentment of results from high-field (500 MHz) 2-D NMR experiments and tandem MS/MS mass spectral sequence analyses. Dolastatin 18 (4) was found to inhibit a selection of cancer cell lines among which GI50 0.39 μg/mL was found for the nonsmall cell lung cancer NCI-H460.