11-Oxoaerothionin: A Cytotoxic Antitumor Bromotyrosine-Derived Alkaloid from the Caribbean Marine Sponge Aplysina lacunosa

Abstract

A new cytotoxic bromotyrosine-derived secondary metabolite, 11-oxoaerothionin [3], was isolated from the Caribbean sea sponge Aplysina lacunosa. The structure of 3 was argued on the basis of detailed spectroscopic analysis and by chemical conversion to the known antibiotic compound 11-hydroxyaerothionin [2]. When screened against a panel of four human cell lines, 11-oxoaerothionin [3] showed pronounced as well as selective antitumor activity toward the human colon (HCT 116) cell line within the limited concentration range of 0.01-0.1 microgram/ml.

Bromoisoxazoline Alkaloids from the Caribbean Sponge Aplysina insularis

“…The n-BuOH soluble fraction of the crude m ethanolic extract of A. insularis gave seven dif ferent bromotyrosine derivatives namely the pre viously described aerophobin-1 (3) (40.3 mg) (Cimino et al, 1983), aerophobin-2 (2) (21.7 mg) (Cimino et al, 1983), aplysinamisin-1 (5) (3.4 mg) (Rodriguez and Pina, 1993), aplysinamisin-2 (6) (9.7 mg) (Rodriguez and Pina, 1993), purealidin L (4) (29.3 mg) (Kobayashi et al, 1995), 2-(3,5-di-brom-4-methoxyphenyl)ethyltrimethylammonium chloride (13) (33.7 mg) (Ciminiello et a l, 1994) and the novel derivative 14-oxo-aerophobin-2 (1) (11.3 mg), while the EtoAc fraction yielded seven more constituents. Except for the quite unusual marine natural product p-hydroxybenzoic acid ethyl ester (ethylparaben) (14) (4.2 mg) the re maining six compounds belong to the group of bromoisoxazoline alkaloids, namely the known de rivatives aerothionin (7) (91.8 mg) (Fattorusso et a l, 1970), 11-oxo-aerothionin (9) (8.0 mg) (Acosta and Rodriguez, 1992), 11-hydroxy-aerothionin (8) (7.4 mg) (Kernan et a l, 1990), fistularin-3 (10) (72.4 mg) (Gopichand and Schmitz, 1979), 11,19-dideoxyfistularin-3 (11) (3.2 mg) (Kernan et a l, 1990) and methyl (6R, 55')-7,9-dibrom-6-hydroxy-8-methoxy-l-oxa-2-azaspiro[4.5]deca-2,7,9-trien-3-carboxylate (12) (3.2 mg) (Ciminiello et a l, 1994).…”

The Marine Bromotyrosine Derivatives

“…3,5-Dibromo-4-(3′-N,N-dimethylaminopropyloxy)cinnamic acid (63) and its ethyl ester (64) were identified from the Caribbean sponge Pseudoceratina crassa by spectroscopic methods and total synthesis (53). LL-PPA216 (65) was first isolated as dextrorota-tory ([α] D + 8.9°) from the sponge Verongia lacunosa collected off the coast of Puerto Rico by Borders et al in 1977 (54), and appeared to be the first bromine compound containing 2-oxazolidone rings isolated from a sponge.…”

Metabólitos secundários das esponjas Aplysina fistularis e Dysidea sp. e atividade antituberculose da 11-cetofistularina-3

“…O extrato metanólico de A. fistularis foi submetido a várias separações cromatográficas (ver Parte Experimental), resultando na obtenção dos derivados da dibromotirosina aeroplisinina-2 (4), 15 2-(3,5-dibromo-4-metoxifenil)-N,N,N-trimetiletanamônio (5), 16 o ácido 7,9-dibromo-10-hidroxi-8-metoxi-1-oxa-2-azaspiro [4.5] deca-2,6,8-trieno-3-carboxílico (6), 17 bem como o éster metílico deste último (7), 18 a 11-oxoaerotionina (8), 19 a aerotionina (9), 20 a 11-ceto-12-hidroxiaerotionina (10), 21 a 11-cetofistularina-3 (11) 22 e a fistularina-3 (12). 23 Todos os derivados da dibromotirosina isolados de A. fistularis coletada na Baía de Todos os Santos foram identificados pela análise de seus dados espectroscópicos e por comparação com dados da literatura, cujas referências para comparação são indicadas para os compostos 4-12 na seção experimental.…”