The Hoiamides, Structurally Intriguing Neurotoxic Lipopeptides from Papua New Guinea Marine Cyanobacteria

Abstract

Two related peptide metabolites, one a cyclic depsipeptide, hoiamide B (2), and the other a linear lipopeptide, hoiamide C (3), were isolated from two different collections of marine cyanobacteria obtained in Papua New Guinea. Their structures were elucidated by combining various techniques in spectroscopy, chromatography and synthetic chemistry. Both metabolites belong to the unique hoiamide structural class, characterized by possessing an acetate extended and S-adenosyl methionine modified isoleucine unit, a central triheterocyclic system comprised of two α-methylated thiazolines and one thiazole, as well as a highly oxygenated and methylated C-15 polyketide unit. In neocortical neurons, the cyclic depsipeptide 2 stimulated sodium influx and suppressed spontaneous Ca2+ oscillations with EC50 values of 3.9 μM and 79.8 nM, respectively, while 3 had no significant effects in these assays.

A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens

“…16,17 Consequently, we have continued to explore the unique secondary metabolites of filamentous marine cyanobacteria for their bioactive constituents, especially those with anticancer, 18 anti-inflammatory 19 and neuromodulatory properties. 20 …”

A Cytotoxic Fellutamide Analogue from the Sponge-Derived Fungus Aspergillus versicolor

“…These lipopeptides were found to have interesting bioactivities, including, anti-inflammatory, antimalarial properties, antimicrobial, antileishmanial, cytotoxic and neurotoxic activities. [1][2][3][4][5][6][7][8][9] Fellutamides A and B are lipopeptides first isolated from the fish-derived fungus Penicillium fellutanum. Fellutamides exhibit cytotoxic properties, 10 and fellutamide A has been shown to stimulate the synthesis and secretion of nerve growth factor (NGF) in vitro.…”

Nichtproteinogene Aminosäurebausteine für Peptidgerüste aus nichtribosomalen Peptiden und hybriden Polyketiden

“…B. in Hoiamid A (41), Schema 13 B) ein 4-Amino-3-hydroxy-2,5-dimethylheptanoat, das von einem NRPS-PKS-Hybridmodul aus den Substraten Ile und Methylmalonyl-CoA gebildet wird. [159] Natürlich kann es auch mehr als einen PKS-vermittelten Kettenverlängerungs-Nichtproteinogene Aminosäuren zyklus geben, um längere Alkylketten aufzubauen. So geht das 3-Amino-2,5,7,8-tetrahydroxy-10-methylundecanoat in den Pahayokoliden aus Cyanobakterien auf Leucin und drei Malonyl-CoA mit entsprechender Justierung der Redoxzustände zurück.…”