Isolation and Structure of Caribenolide I, a Highly Potent Antitumor Macrolide from a Cultured Free-Swimming Caribbean Dinoflagellate, Amphidinium sp. S1-36-5

Autor: Laurie Cornell, Judy MacBeth, Stella Huang, Lucie Maranda, Yuzuru Shimizu, Ines Bauer, Kurt A. Young, Craig R. Fairchild
Rok vydání: 1995
Předmět:
Zdroj: The Journal of Organic Chemistry. 60:1084-1086
ISSN: 1520-6904
0022-3263
Popis: A large number of highly active antitumor compounds have been found in marine organisms, especially in invertebrates. In most cases, however, the yields of these potentially important compounds as therapeutic agents are prohibitively low. On the other hand, there is the speculation that some of the animal constituents have their origins in microalgae, which may serve as culturable sources of the c0mpounds.l In our screening efforts t o find such progenitors, potent antineoplastic activity was discovered in the cell extract of a free-swimming dinoflagellate isolated from the water at Brewers Bay, St. Thomas, US Virgin Islands. A single-cell isolate of the organism, Amphid in ium sp. S1-36-5, was cultivated in enriched seawater, K-medi~ m , ~ under fluorescent illumination, and the cells were harvested at the stationary phase. The freeze-dried cells were extracted with a mixture of toluene and methanol (3:1), and the extract was partitioned between 90% methanol and n-hexane. The 90% aqueous methanol fraction, which had shown strong cytotoxic activity (IC50 0.35 pg/mL) against human colon tumor cell line HCT 116, was chromatographed successively on silica gel with methylene chloride-methanol (9551, C18 silica gel with 80% aqueous acetonitrile, Hamilton PRP-1 with 80% aqueous acetonitrile, and Econosil CN (Alltech) with isooctane-2-propanol 8:l to afford a pure active compound (named caribenolide I) in a 0.026% yield from the dried cells. Caribenolide I (1) was obtained as a colorless amorphous or microcrystalline solid, [ a ] 2 5 ~ = +91.4 f 0.8" (c = 0.13, CH2C12). High resolution mass spectroscopy (HRFABMS) suggested a molecular formula of C33H52011, which was consistent with the carbon and hydrogen numbers counted in the NMR spectra. The compound has no UV maximum above 200 nm, indicating the absence of a conjugated system.
Databáze: OpenAIRE
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