Dinoflagellate-Related Amphidinolides from the Brazilian Octocoral Stragulum bicolor

Abstract

Benthic cnidarians are colonial marine animals that host a rich population of associated and symbiotic microorganisms. In a recent paper we described for the first time the isolation of amphidinolide P (1) from the Brazilian octocoral Stragulum bicolor. Amphidinolides and similar compounds had been previously reported only from dinoflagellates of the genus Amphidinium; thus the presence of 1 in the invertebrate opens intriguing questions on the role and occurrence of these molecules in marine ecosystems. Here we report the identification of four further amphidinolides from the same soft coral, including the known amphidinolide T1 (2) and the new analogues here named amphidinolides C4 (3), B8 (4), and B9 (5). The chemical structures have been elucidated mainly by extensive study of spectroscopic data. Cytotoxic activities of 3 and 4 were evaluated against the colon adenocarcinoma cell line HCT-116.

Potent Cytotoxic Analogs of Amphidinolides from the Atlantic Octocoral Stragulum bicolor

“…This dry extract (700 mg) was resuspended in 2 mL water and fractionated on 6.5 g HR-X resin. As reported in the previous work [19] preliminary LC-MS and NMR analyses of CH 3 CN/H 2 O (7:3) fraction (18.2 mg) and CH 3 CN (11.9, mg) showed the presence of amphidinolide derivatives and other minor related compounds. HPLC purification of the first fractions on C18 column with a gradient of CH 3 CN/H 2 O led to the isolation of amphidinolides B8, B9 and C4, together with new compounds stragulin A ( 4 , 0.3 mg) and amphidinolide PX1 ( 1 , 0.1 mg); whereas purification of the second fraction gave, along with the known amphidinolide P and T1, the new amphidinolides PX2 ( 2 , 0.3 mg) and PX3 ( 3 , 0.3 mg).…”

“…Together with similar macrolides reported with other names (amphidinolactones, iriomoteolides and caribenolide I) [9,10,11,12,13] and related linear polyketides (e.g., amphidinins) [14,15,16,17], AMPs are produced by dinoflagellates of the genus Amphidinium . Recently, we have reported the extraction of a number of amphidinolides from the softcoral Stragulum bicolor [18,19], including the known amphidinolide P and T1 and three new analogues named amphidinolide C4, B8 and B9 according to the structural relationship with other known members of the family. Here we describe the full characterization of three new cytotoxic members of the AMP family ( 1 – 3 ), together with the linear polyketide stragulin A ( 4 ) that showed cytotoxic activity at sub-micromolar scale against melanoma cells.…”

Marine natural products

“…New examples of amphidinolides, C4 1022, B8 1023 and B9 1024, in addition to the known dinoagellatesourced T1, were reported from Brazilian specimens of the octocoral Stragulum bicolor. 596 Modest cytotoxicity was observed for 1022 and 1023. The simple dinormonoterpenes 1025 and 1026 were reported from Sinularia mollis.…”

The Tetrahydrofuran Motif in Polyketide Marine Drugs

“…Toxicity was tested against the colon adenocarcinoma cell line HCT-116, finding an IC50 of 10.3 µM. Compound 5 is therefore surprisingly inactive, although it contains a hydroxyl group in the side chain [14]. The interesting biological properties of these compounds have attracted the attention of different authors who have described either total syntheses [15,16] or synthetic approaches to various molecular fragments [17][18][19].…”