Bryan Sakamoto

Halogenated Fatty Acid Amides and Cyclic Depsipeptides from an Eastern Caribbean Collection of the Cyanobacterium Lyngbya majuscula

A lipophilic extract of an eastern Caribbean collection of Lyngbya majuscula yielded two new halogenated fatty acid amides, grenadamides B (1) and C (2), and two new depsipeptides, itralamides A (3) and B (4), along with the known compounds hectochlorin and deacetylhectochlorin. The recently reported depsipeptide carriebowmide (5) was also present in the extract and isolated as its sulfone artifact (6). Compounds 1-4 were identified by spectroscopic methods. The configurations of the amino acid residues of 3, 4, and 6 were determined by LC-MS analyses of diastereomeric derivatives of the acid hydrolysates (advanced Marfeys method). Based on the configurational analysis of 6, in direct comparison with authentic carriebowmide (5), a minor structural revision of 5 is proposed. Compounds 1 and 2 displayed marginal activity against the beet armyworm (Spodoptera exigua). Compounds 1-4 and 6 were assessed for general cell toxicity in human embryonic kidney (HEK293) cells. Only itralamide B (4) displayed significant cytotoxicity, showing an IC(50) value of 6 +/- 1 muM.

A new lyngbyatoxin from the Hawaiian cyanobacterium Moorea producens.

Lyngbyatoxin A from the marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) is known as the causative agent of “swimmer’s itch” with its highly inflammatory effect. A new toxic compound was isolated along with lyngbyatoxin A from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies revealed the isolated compound had the same planar structure with that of lyngbyatoxin A. The results of optical rotation and CD spectra indicated that the compound was a new lyngbyatoxin A derivative, 12-epi-lyngbyatoxin A (1). While 12-epi-lyngbyatoxin A showed comparable toxicities with lyngbyatoxin A in cytotoxicity and crustacean lethality tests, it showed more than 100 times lower affinity for protein kinase Cδ (PKCδ) using the PKCδ-C1B peptide when compared to lyngbyatoxin A.

Manauealide C and Anhydrodebromoaplysiatoxin, Toxic Constituents of the Hawaiian Red Alga, Gracilaria coronopifolia

Manauealide C (1) and anhydrodebromoaplysiatoxin (4), toxic constituents of the Hawaiian red alga, Gracilaria coronopifolia which has been concerned with food poisoning cases, were studied. The absolute structure of manauealide C was determined as 1 by chemical conversion and spectroscopic methods. The first complete assignment of (13)C chemical shifts for anhydrodebromoaplysiatoxin (4) was established. The biological activity of 4 was also investigated.

ISOLATION OF A SULFOQUINOVOSYL MONOACYLGLYCEROL FROM BRYOPSIS SP. (CHLOROPHYTA): IDENTIFICATION OF A FACTOR CAUSING A POSSIBLE SPECIES-SPECIFIC ECDYSIS RESPONSE IN GAMBIERDISCUS TOXICUS (DINOPHYCEAE)1,

A bioactive compound that induced ecdysis (thecal loss) in Gambierdiscus toxicus Adachi et Fukuyo (Dinophyceae) cultures was isolated from a host macroalga, Bryopsis sp. (Chlorophyta). The ecdysis factor was identified by spectroscopic methods as 1‐O‐palmitoyl‐3‐O‐(6′‐sulfo‐α‐d‐quinovopyranosyl)‐sn‐glycerol (PSQG). From our results, PSQG induced ecdysis at a high frequency and appeared not to inhibit the growth of G. toxicus cultures. The induction of ecdysis followed a dose‐dependent saturation curve from 4 to 8 μM PSQG. To determine specificity of PSQG, the effects of palmitoyl‐l‐α‐lysophosphatidylcholine (PLPC) were observed. Because PLPC contains a lipophilic palmitoyl moiety and hydrophilic phosphatidyl choline group, the compound possesses a detergent‐like amphiphathic property similar to PSQG. Our results demonstrate that PLPC induced ecdysis at a high frequency in G. toxicus cultures and generated a similar dose–response curve as PSQG. The ecdysis activity observed in PSQG and PLPC may correlate with the detergent‐like amphiphathic property of both compounds. Although PLPC induced a similar ecdysis response as PSQG, PLPC appeared to inhibit the growth of G. toxicus cultures. Preliminary results on the effects of PSQG on the dinoflagellates Prorocentrum lima (Ehrenberg) Dodge and Coolia monotis Meunier did not parallel the results observed in G. toxicus. This study demonstrated the existence of a factor from Bryopsis sp. that elicited a possible species‐specific ecdysis response in G. toxicus cultures. This is the first report of a compound that induced ecdysis in G. toxicus or in any dinoflagellate.

Two new lyngbyatoxin derivatives from the Cyanobacterium, Moorea producens.

The toxin-producing cyanobacterium, Moorea producens, is a known causative organism of food poisoning and seaweed dermatitis (also known as “swimmer’s itch”). Two new toxic compounds were isolated and structurally elucidated from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies, as well as optical rotations and CD spectra indicated two new lyngbyatoxin derivatives, 2-oxo-3(R)-hydroxy-lyngbyatoxin A (1) and 2-oxo-3(R)-hydroxy-13-N-desmethyl-lyngbyatoxin A (2). The cytotoxicity and lethal activities of 1 and 2 were approximately 10- to 150-times less potent than lyngbyatoxin A. Additionally, the binding activities of 1 and 2 possessed 10,000-times lower affinity for the protein kinase Cδ (PKCδ)-C1B peptide when compared to lyngbyatoxin A. These findings suggest that these new lyngbyatoxin derivatives may mediate their acute toxicities through a non-PKC activation pathway.

A new malyngamide from the marine cyanobacterium Moorea producens

Abstract A new malyngamide (1) was isolated along with seven known compounds (2–8) from the marine cyanobacterium Moorea producens collected in Hawaii. Compound 1 represented the first reported malyngamide with a hydroxy moiety at C-7 of the characteristic fatty acid portion of the compound. Compound 1 showed cytotoxicity against L1210 cell line at an IC50 value of 2.9 mM and lethal toxicity against the shrimp Palaemon paucidens at a LD100 value of 33.3 mg/kg. The bioactivity of compound 1 was approximately 10–100 times weaker than those of isomalyngamides A and B (3, 4). These results indicated that the methoxy group at C-7 of the fatty acid section confers a degree of bioactivity in malyngamides.