Isolation of Latrunculin A, 6,7-Epoxylatrunculin A, Fijianolide A, and Euryfuran from a New Genus of the Family Thorectidae

Journal of Natural Products
1992.0

Abstract

Latrunculin A, 6,7-epoxylatrunculin A, euryfuran [l], and fijianolide A have been isolated froma new genus ofa Pacific sponge in the family Thorectidae. Their structures were identified by comparison with the literature data. Our ongoing studies of marine-derived biologically active metabolites led us to investigate a new genus of the marine sponge family Thorectidae. Here we report the unusual co-occurrence of latrunculin A (14, fijianolide A (5,6), euryfuran (71, and 6,7-epoxylatrunculin A (4) in the same sponge. To the best of our knowledge, this is the first report of the isolation of 6,7-epoxylatrunculin A from a sponge other than Lutrunculia mgnifica Keller (4), which contained latrunculins A-D. Latrunculin A has also been reported from nudibranchs: Chrmdwis elizabethim (8), Glossidwis quadricolor (9), Cbromodwis williani (6), Cbromodwis sp. (6), and Cbromodoris lochi (3) associated with Spongia mycofijiensis. LatrunculinA(O.l2% wetwtsponge) was isolated as the major metabolite of this sponge. The structure was identified by comparison of nmr data with those previously reported for latrunculin A (1,2,4). In our hands, latrunculin A inhibits the in vitro proliferation of the cultured murine P388 leukemia cells with an ICs, of 4.1 pg/ml. The growth of Candiah albicans is also inhibited by the compound with MIC value of 15.6 pgl ml. Latrunculin A inhibited the adherence of PMA-(phorbol-l2-myristate- 13 acetate) induced EL-4.IL-2 murine lymphomacells (50% inhibition at 0.125 pg/ml) in an assay which is used to detect agonists/antagonists of protein kinase C (PKC) (10).Euryfuran1 was isolated as the second major compound. We report here the complete as-signments of the 'H- and '3C-nmr data for euryfuran. This is the first report of the complete assignments of the 13C data for euryfuran, although it has been isolated from Eutyspongia sp. (7) and has been synthesized (11-15). The 'H and 13C assignments were based on the results from COSY (16), HETCORR (17), and HMBC (1 8) experiments. Euryfuran was unstableinCDC1, anddecomposed within a week in the freezer. The absolute stereochemistry of euryfuran, [ct]23D -21.6' (CHCI,, c=0.16), was deduced based on the rotation reported for (+ )-euryfuran, [a]~ + 19" (CHCl,, c= 1.0) that was obtained by a total synthesis (1 5). Fijianolide A and 6,7-epoxylatrunculin A were isolated as minor compounds. Fijianolide A has been isolated from Spongia mycofijiensis (5), Hyattella sp. (6) and also from the nudibranch predator C. lochi (6). Euryfuran, 6,7 epoxylatrunculin A, and fijianolide A inhibit the in vitro proliferation of the cultured human lung cancer cell line A549withIC,,valuesof 1.5,0.2,and 1.4 pg/ml, respectively, and the murine P388leukemia cells with IC,, values of 1.6, 1.8, and 1.0 pg/ml, respectively. 6,7- Epoxylatrunculin Aand fijianolide A also inhibit the growth of Candida albicans with MIC values of 25 and 6.2 pg/ml, respectively. Both euryfuran and 6,7 epoxylatrunculin A inhibited the PMAinduced adherence ofEL-4.L-2 cells (48% inhibition at 0.025 pg/ml and 100% inhibition at 0.003 pg/ml, respectively). However, fijianolide A induced a significant adherence of EL-4.L-2 cells in the absence of PMA (0.003-0.025 pg/ml) indicative PKC agonistic activity.

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