Credneramides A and B: neuromodulatory phenethylamine and isopentylamine derivatives of a vinyl chloride-containing fatty acid from cf. Trichodesmium sp. nov

Abstract

Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (1, IC(50) 4.0 μM; 2, IC(50) 3.8 μM).

Figure 1

Key COSY, HMBC, and ROE correlations of credneramides A (1) and B (2).

Figure 2

Evolutionary tree of the credneramide-producing strain PNG-05/19/05-13. The phylogenetic proximity with the genus Trichodesmium (reference/type-strains = Trichodesmium erythraeum IMS) suggests that this strain represents a new taxa within this genus, which would also include the related and morphologically-similar strains PAL08-3.2 (GenBank acc. Nr. HM585025) and NAC8-50 (GenBank acc. Nr. GU724203) previously putatively identified as cf. Oscillatoria sp. Representative reference-strains obtained from Bergey’s Manual are highlighted with asterisks (*) and the sensu stricto for the genera Trichodesmium and Oscillatoria are highlighted with green boxes. In addition to the strain PNG-05/19/05-13, credneric acid (3) was also isolated from the Panamanian strain cf. Oscillatoria sp. PAC-17-FEB-10-3 (both credneric acid-producing strains are highlighted with red arrows). The cladogram is based on SSU (16S) rRNA gene sequences using the bayesian (MrBayes) method and the support values are indicated as posterior probability at the nodes. The specimens are indicated as species, strain, and access number in brackets. The scale bar is indicated at 0.04 expected nucleotide substitutions per site.

Figure 3

Calcium oscillation inhibition in cerebrocortical mouse neurons by credneramides A (1) (IC₅₀ 4.0 μM) and B (2) (IC₅₀ 3.8 μM).