Thermoactinoamide A, an Antibiotic Lipophilic Cyclopeptide from the Icelandic Thermophilic Bacterium <i>Thermoactinomyces vulgaris</i>

The thermophilic bacterium <i>Thermoactinomyces vulgaris</i> strain ISCAR 2354, isolated from a coastal hydrothermal vent in Iceland, was shown to contain thermoactinoamide A (<b>1</b>), a new cyclic hexapeptide composed of mixed d and l amino acids, along with five minor analogues (<b>2</b>–<b>6</b>). The structure of <b>1</b> was determined by one- and two-dimensional NMR spectroscopy, high-resolution tandem mass spectrometry, and advanced Marfey’s analysis of <b>1</b> and of the products of its partial hydrolysis. Thermoactinoamide A inhibited the growth of <i>Staphylococcus aureus</i> ATCC 6538 with an MIC value of 35 μM. On the basis of literature data and this work, cyclic hexapeptides with mixed d/l configurations, one aromatic amino acid residue, and a prevalence of lipophilic residues can be seen as a starting point to define a new, easily accessible scaffold in the search for new antibiotic agents

Chloromethylhalicyclamine B, a Marine-Derived Protein Kinase CK1δ/ε Inhibitor

The halogenated alkaloid chloromethylhalicyclamine B (<b>1</b>), together with the known natural compound halicyclamine B (<b>2</b>), was isolated from the extract of the sponge <i>Acanthostrongylophora ingens</i>. The structure of compound <b>1</b> was determined by spectroscopic means, and it was shown that <b>1</b> is produced by reaction of <b>2</b> with CH₂Cl₂ used for extraction. Compound <b>1</b> was a selective CK1δ/ε inhibitor with an IC₅₀ of 6 μM, while the natural compound <b>2</b> was inactive. The absolute configuration of <b>1</b> was determined by quantum mechanical calculation of its ECD spectrum, and this also determined the previously unknown absolute configuration of the parent halicyclamine B (<b>2</b>). Computational studies, validated by NOESY data, showed that compound <b>1</b> can efficiently interact with the ATP-binding site of CK1δ in spite of its globular structure, very different from the planar structure of known inhibitors of CK1δ. This opens the way to the design of a new structural type of CK1δ/ε inhibitors

Biologically Active Acetylenic Amino Alcohol and <i>N</i>‑Hydroxylated 1,2,3,4-Tetrahydro-β-carboline Constituents of the New Zealand Ascidian <i>Pseudodistoma opacum</i>

The first occurrence of an acetylenic 1-amino-2-alcohol, distaminolyne A (<b>1</b>), isolated from the New Zealand ascidian <i>Pseudodistoma opacum</i>, is reported. The isolation and structure elucidation of <b>1</b> and assignment of absolute configuration using the exciton coupled circular dichroism technique are described. In addition, a new N-9 hydroxy analogue (<b>2</b>) of the known <i>P. opacum</i> metabolite 7-bromohomotrypargine is also reported. Antimicrobial screening identified modest activity of <b>1</b> toward <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Mycobacterim tuberculosis</i>, while <b>2</b> exhibited a moderate antimalarial activity (IC₅₀ 3.82 μM) toward a chloroquine-resistant strain (FcB1) of <i>Plasmodium falciparum</i>

Antifouling 26,27-Cyclosterols from the Vietnamese Marine Sponge <i>Xestospongia testudinaria</i>

Three new C₂₉ sterols with a cyclopropane ring cyclized between C-26 and C-27 of the side chain, aragusterol I (<b>1</b>), 21-<i>O</i>-octadecanoyl-xestokerol A (<b>4</b>), and 7β-hydroxypetrosterol (<b>5b</b>), were isolated from the Vietnamese marine sponge <i>Xestospongia testudinaria</i>, along with the known compounds, aragusterol B (<b>2</b>), xestokerol A (<b>3</b>), 7α-hydroxypetrosterol (<b>5a</b>), 7-oxopetrosterol (<b>6</b>), and petrosterol (<b>7</b>). The structures of the new compounds were established by analysis of spectroscopic data including 1D and 2D NMR, and high-resolution electrospray ionization mass spectrometry (HRESIMS). Their capacity to inhibit the adhesion of isolated bacteria from marine biofilms was evaluated against the bacterial strains <i>Pseudoalteromonas</i> sp. D41, <i>Pseudoalteromonas</i> sp. TC8, and <i>Polaribacter</i> sp. TC5. Aragusterol B (<b>2</b>) and 21-<i>O</i>-octadecanoyl-xestokerol A (<b>4</b>) exhibited the most potent antifouling activity with EC₅₀ values close to these reported in the literature for tributyltin oxide, a marine anti-biofouling agent now considered to be a severe marine pollutant. Due to its comparable activity to tributyltin oxide and its absence of toxicity, the new 26,27-cyclosterol, 21-<i>O</i>-octadecanoyl-xestokerol A (<b>4</b>) constitutes a promising scaffold for further investigations