https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Antimycobacterial natural products

Natural antimycobacterial metabolites: current status.

The marine environment is a seemingly inexhaustible treasury of organisms whose secondary metabolites bear witness to the lavishness and inventiveness with which nature is able to manipulate molecular architecture. But to what purpose are these diverse and often grotesque compounds produced? This review is founded on the premise that some of them may be involved in the uptake and transport of metal ions present in the aquatic milieu. Many metabolites produced by terrestrial organisms are known to act as ionophores, but the case for similar behavior by their marine counterparts is far hazier. Notwithstanding the relative abundance of certain metal ions in the oceans, and of metabolite structures possessing features that should facilitate the chelation of metal ions, few attempts to establish a connection between these two phenomena have been reported. We have whittled down the voluminous literature of natural products derived from marine sources to expose a core of observations and speculations germane to our premise. These facts and fantasies are evaluated in this review. A mere handful of metal-containing complexes has actually been isolated; furthermore, attempts to prepare such complexes in vitro are rare, and spectroscopic evidence for metal–metabolite interactions, whether in vivo or in vitro, is not common. Only with the vanadium-sequestering tunichromes does a logical (but by no means complete) picture begin to emerge. In several other cases, the plausibility of metal chelation, though mooted by authors, remains unsupported by experimental evidence. However, continuing efforts to obtain structural, and particularly conformational, information on the metabolites by means of X-ray crystallography, nuclear magnetic resonance spectroscopy, and molecular mechanics calculations would seem to provide the key to a rational approach to this neglected topic. On the basis of recent studies dealing with such structural aspects, we present a selection of candidate compounds, some of which are the targets of our own synthetic attentions, whose potential for binding to metal cations merits further research.

Marine Metabolites and Metal Ion Chelation: The Facts and the Fantasies

Two novel antimicrobial tetrapeptide-like substances, halocyamine A and B, were isolated from the solitary ascidian Halocynthia roretzi by a procedure including extraction steps, chromatographies on coarse and fine HP-20 columns, and preparative reversed-phase high-performance liquid chromatography. The structures of halocyamine A and B were determined to be L-histidyl-L-6,7-dihydroxyphenylalanylglycyl-6-bromo-8,9-didehy drotryptamine and L-threonyl-L-6,7-dihydroxyphenylalanyl-L-histidyl-6-bromo-8,9- didehydrotryptamine, respectively, by spectral analyses and degradation studies. Besides antimicrobial activities against several kinds of bacteria and yeasts, both of them showed cytotoxic activities against neuronal cells cultured from rat fetal brain, mouse neuroblastoma N-18 cells, and human hepatoma Hep-G2 cells. They were only detected in the "morula"-like cells, which are of the most abundant cell type among the hemocytes of H. roretzi.

Jun'ichi Kobayash

Papers

Ascididemin, a novel pentacyclic aromatic alkaloid with potent antileukemic activity from the Okinawan tunicate Didemnum sp.