Bouillonamide: A Mixed Polyketide–Peptide Cytotoxin from the Marine Cyanobacterium Moorea bouillonii

Abstract

The tropical marine cyanobacterium, Moorea bouillonii, has gained recent attention as a rich source of bioactive natural products. Continued chemical investigation of this cyanobacterium, collected from New Britain, Papua New Guinea, yielded a novel cytotoxic cyclic depsipeptide, bouillonamide (1), along with previously reported molecules, ulongamide A and apratoxin A. Planar structure of bouillonamide was established by extensive 1D and 2D NMR experiments, including multi-edited HSQC, TOCSY, HBMC, and ROESY experiments. In addition to the presence of α-amino acid residues, compound 1 contained two unique polyketide-derived moieties, namely a 2-methyl-6-methylamino-hex-5-enoic acid (Mmaha) residue and a unit of 3-methyl-5-hydroxy-heptanoic acid (Mhha). Absolute stereochemistry of the α-amino acid units in bouillonamide was determined mainly by Marfey’s analysis. Compound 1 exhibited mild toxicity with IC50’s of 6.0 µM against the neuron 2a mouse neuroblastoma cells.

The cytotoxic activities of the ethyl acetate and butanol crude extracts of marine cyanobacteria collected from Udar Island, Malaysia

“…collected from Udar Island is rich in secondary metabolites, which are mainly peptides. The observed mass of Apratoxin A from the sample was similar to the Moorea bouilonii samples collected from Guam, Palau, Papua New Guinea, and Malaysia (Lopez et al, 2017;Matthew et al, 2010;Tan et al, 2013). In other words, Apratoxin A has been frequently observed from Moorea bouilonii samples.…”

Microalgae as a source of high-value bioactive compounds

“…In comparison to only a few secondary metabolites from ribosomal proteins, a range of cyanobacterial bioactive secondary metabolites is produced via polyketide synthase (PKS) and non-ribosomal peptide synthase (81). The hybrid polyketide-polypeptide structural class of molecules, are characterized by some unique structural features, such as the incorporation of modified amino/hydroxyl acids, heteroaromatic ring systems, as well as extended polyketide-derived units (87). The extended polyketide derived units can be either linear or undergo cyclization to form a common scaffold, like pyrrolidone rings in the Jamaicamides.…”

Introduction to the Analysis of Bioactive Compounds in Marine Samples

“…About two-fifths of new marine bioactive compounds are derived from microorganisms, including bacteria, microalgae, and fungi, and about one-fifth of the new bioactive compounds are from other marine sources such as fish processing waste and ascidian (tunicates). [8][9][10][11][12][13][14][15][16] of bioactive natural products from sources such as bacteria, fungi, sponge, microalgae, starfish, algae, ascidian and fish waste. There are several reviews covering the marine natural products from differences sources [7,[17][18][19][20][21].…”

“…)mixed polyketide cytotoxin, isolated from the marine cyanobacterium Moorea bouillonii, showed a mild toxicity against neuro-2a mouse neuroblastoma cells[11].…”