Depsipeptide companeramides from a Panamanian marine cyanobacterium associated with the coibamide producer.

Two new cyclic depsipeptides, companeramides A (1) and B (2), have been isolated from the phylogenetically characterized cyanobacterial collection that yielded the previously reported cancer cell toxin coibamide A (collected from Coiba Island, Panama). The planar structures of the companeramides, which contain 3-amino-2-methyl-7-octynoic acid (Amoya), hydroxy isovaleric acid (Hiva), and eight α-amino acid units, were established by NMR spectroscopy and mass spectrometry. The absolute configuration of each companeramide was assigned using a combination of Marfey's methodology and chiral-phase HPLC analysis of complete and partial hydrolysis products compared to commercial and synthesized standards. Companeramides A (1) and B (2) showed high nanomolar in vitro antiplasmodial activity but were not overtly cytotoxic to four human cancer cell lines at the doses tested.

Santacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp.

A dark brown tuft-forming cyanobacterium, morphologically resembling the genus Symploca, was collected during an expedition to the Coiba National Park, a UNESCO World Heritage Site on the Pacific coast of Panama. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it is 4.5% divergent from the type strain for Symploca and thus is likely a new genus. Fractionation of the crude extract led to the isolation of a new cytotoxin, designated santacruzamate A (1), which has several structural features in common with suberoylanilide hydroxamic acid [(2), SAHA, trade name Vorinostat], a clinically approved histone deacetylase (HDAC) inhibitor used to treat refractory cutaneous T-cell lymphoma. Recognition of the structural similarly of 1 and SAHA led to the characterization of santacruzamate A as a picomolar level selective inhibitor of HDAC2, a Class I HDAC, with relatively little inhibition of HDAC4 or HDAC6, both Class II HDACs. As a result, chemical syntheses of santacruzamate A as well as a structurally intriguing hybrid molecule, which blends aspects of both agents (1 and 2), were achieved and evaluated for their HDAC activity and specificity.

Hydroxyalkenylresorcinols from Stylogyne turbacensis.

Two new compounds, 5-(11'(S)-hydroxy-8'-heptadecenyl)resorcinol (3) and 5-(12'(S)-hydroxy-8',14'-heptadecadienyl)resorcinol (4), were isolated from the leaves of Stylogyne turbacensis together with the known analogue metabolites 1 and 2. Compounds 3 and 4 showed the strongest activity in the leishmania assay, 7 and 3 microM, respectively, while compounds 1, 2, and 4 showed moderate activity against a drug-resistant strain of Trypanosoma cruzi with IC(50) values of 30, 25, and 22 microM, respectively. Additional testing in MCF-7 and NCI-H460 was performed for compounds 3 and 4. The structures of compounds 1-4 were elucidated using NMR, MS, and other spectroscopic data. The absolute stereochemistry of compounds 3 and 4 was also investigated using the Mosher ester approach. Peracetylated derivatives of these four metabolites were produced and their activities determined in the Trypanosoma cruzi assay.

Antimalarial linear lipopeptides from a Panamanian strain of the marine cyanobacterium Lyngbya majuscula.

As part of the Panama International Cooperative Biodiversity Groups (ICBG) project, two new (2, 4) and two known (1, 3) linear alkynoic lipopeptides have been isolated from a Panamanian strain of the marine cyanobacterium Lyngbya majuscula. Carmabin A (1), dragomabin (2), and dragonamide A (3) showed good antimalarial activity (IC50 4.3, 6.0, and 7.7 microM, respectively), whereas the nonaromatic analogue, dragonamide B (4), was inactive. The planar structures of all four compounds were determined by NMR spectroscopy in combination with mass spectrometry, and their stereoconfigurations were established by chiral HPLC and by comparison of their optical rotations and NMR data with literature values.