4 research outputs found
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 CH<sub>2</sub>Cl<sub>2</sub> used
for extraction. Compound <b>1</b> was a selective CK1δ/ε
inhibitor with an IC<sub>50</sub> 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 (IC<sub>50</sub> 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 C<sub>29</sub> 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 EC<sub>50</sub> 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