15 research outputs found
Cytotoxic Lignans from Fruits of <i>Cleistanthus indochinensis</i>: Synthesis of Cleistantoxin Derivatives
Two new aryl-tetralin lignans, <b>1</b> and <b>2</b>, were isolated from the fruits of <i>Cleistanthus indochinensis</i> by bioassay-guided purification. Their structures were determined
by spectroscopic analysis including MS and 2D NMR. The absolute configurations
of <b>1</b> and <b>2</b> were established from examination
of their CD spectra. Compound <b>1</b> was cytotoxic against
KB cells with an IC<sub>50</sub> value of 0.022 μM, while compound <b>2</b> had weaker cytotoxicity, with an IC<sub>50</sub> value of
1.4 μM. When tested against other cancer cell lines (MCF-7,
MCF-7R, and HT29), <b>1</b> showed an IC<sub>50</sub> of 0.014
against MCF-7R cells and an IC<sub>50</sub> of 0.036 μM against
MCF-7 cells. A series of amide derivatives of a new lactone, homoderivatives
of <b>1</b>, were prepared. Of these derivatives, only compound <b>3</b> had weak cytotoxicity against KB cells
Cytotoxic Lignans from Fruits of <i>Cleistanthus indochinensis</i>: Synthesis of Cleistantoxin Derivatives
Two new aryl-tetralin lignans, <b>1</b> and <b>2</b>, were isolated from the fruits of <i>Cleistanthus indochinensis</i> by bioassay-guided purification. Their structures were determined
by spectroscopic analysis including MS and 2D NMR. The absolute configurations
of <b>1</b> and <b>2</b> were established from examination
of their CD spectra. Compound <b>1</b> was cytotoxic against
KB cells with an IC<sub>50</sub> value of 0.022 μM, while compound <b>2</b> had weaker cytotoxicity, with an IC<sub>50</sub> value of
1.4 μM. When tested against other cancer cell lines (MCF-7,
MCF-7R, and HT29), <b>1</b> showed an IC<sub>50</sub> of 0.014
against MCF-7R cells and an IC<sub>50</sub> of 0.036 μM against
MCF-7 cells. A series of amide derivatives of a new lactone, homoderivatives
of <b>1</b>, were prepared. Of these derivatives, only compound <b>3</b> had weak cytotoxicity against KB cells
Acetylcholinesterase Inhibitors from the Leaves of <i>Macaranga kurzii</i>
Bioassay-guided fractionation of an extract of leaves
of <i>Macaranga kurzii</i> yielded four new compounds, a
stilbene
(furanokurzin, <b>1</b>) and three flavonoids (macakurzin A–C, <b>2</b>–<b>4</b>). Nine known compounds were also isolated
(<b>5</b>–<b>13</b>). Their structures were determined
by spectroscopic analyses including MS and 2D NMR. The isolates were
all evaluated for acetylcholinesterase inhibitory activity. Compound <b>6</b> (<i>trans</i>-3,5-dimethoxystilbene) exhibited
the greatest activity (IC<sub>50</sub> 9 μM). Cytotoxic evaluation
against KB cells showed that compound <b>7</b> had an IC<sub>50</sub> of 4 μM, followed by <b>11</b> (IC<sub>50</sub> 10 μM) and <b>3</b> (IC<sub>50</sub> 13 μM)
Two new linear acetogenins from the fruits of <i>Goniothalamus gracilipes</i>
<p>Two new linear acetogenins, gracilipin A (<b>1</b>) and methylsaccopetrin A (<b>2</b>) along with seven known compounds, saccopetrin A (<b>3</b>), 7,3′,4′-trimethylquercetin (<b>4</b>), rhamnazin (<b>5</b>), casticin (<b>6</b>), isokanugin (<b>7</b>), melisimplexin (<b>8</b>) and 5-hydroxy-3,7-dimethoxy-3′,4′-methylenedioxyflavone (<b>9</b>) were isolated from the fruits of <i>Goniothalamus gracilipes</i> Bân. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR, 2D-NMR and circular dichroism (CD). Compounds <b>1</b> and <b>3</b> showed cytotoxic activity against KB cell line with IC<sub>50</sub> values of 14.6 and 15.3 μM, respectively.</p
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
Structural formulae of Artemisinin and synthetic derivatives belonging to the first category AJ.
<p>Structural formulae of Artemisinin and synthetic derivatives belonging to the first category AJ.</p
Endiandric Acid Analogues from Beilschmiedia ferruginea as Dual Inhibitors of Bcl-xL/Bak and Mcl-1/Bid Interactions
A rapid screening by <sup>1</sup>H and <sup>1</sup>H–<sup>13</sup>C HSQC NMR spectroscopy of
EtOAc extracts of Endiandra and Beilschmiedia species allowed the selection of Beilschmiedia ferruginea leaves and flowers extract
for a chemical investigation, leading
to the isolation of 11 new tetracyclic endiandric acid analogues,
named ferrugineic acids A–K (<b>1</b>–<b>11</b>). Their structures were determined by 1D and 2D NMR spectroscopic
analysis in combination with HRMS data. These compounds were assayed
for Bcl-xL and Mcl-1 binding affinities. Ferrugineic acids B, C, and
J (<b>2</b>, <b>3</b>, and <b>10)</b> exhibited
significant binding affinity for both antiapoptotic proteins Bcl-xL
(<i>K</i><sub>i</sub> = 19.2, 12.6, and 19.4 μM, respectively)
and Mcl-1 (<i>K</i><sub>i</sub> = 14.0, 13.0, and 5.2 μM,
respectively), and ferrugineic acid D (<b>4</b>) showed only
significant inhibiting activity for Mcl-1 (<i>K</i><sub>i</sub> = 5.9 μM)
<i>In vitro</i> anti-HCV activity of Artemisinin and its selected analogues on the replication of infectious HCVcc as measured by means of qRT-PCR (n = 4).
<p>a) ART; b) TVN4; c) AJ-002 and d) AJ-004. Bars indicate the HCV RNA level as compared to control (%) and lines represent the cell growth as compared to untreated controls (%).</p
Integration of Molecular Networking and <i>In-Silico</i> MS/MS Fragmentation for Natural Products Dereplication
Dereplication
represents a key step for rapidly identifying known
secondary metabolites in complex biological matrices. In this context,
liquid-chromatography coupled to high resolution mass spectrometry
(LC-HRMS) is increasingly used and, via untargeted data-dependent
MS/MS experiments, massive amounts of detailed information on the
chemical composition of crude extracts can be generated. An efficient
exploitation of such data sets requires automated data treatment and
access to dedicated fragmentation databases. Various novel bioinformatics
approaches such as molecular networking (MN) and <i>in-silico</i> fragmentation tools have emerged recently and provide new perspective
for early metabolite identification in natural products (NPs) research.
Here we propose an innovative dereplication strategy based on the
combination of MN with an extensive <i>in-silico</i> MS/MS
fragmentation database of NPs. Using two case studies, we demonstrate
that this combined approach offers a powerful tool to navigate through
the chemistry of complex NPs extracts, dereplicate metabolites, and
annotate analogues of database entries
Structural formulae of Artemisinin and synthetic derivatives belonging to the second category TVN.
<p>Structural formulae of Artemisinin and synthetic derivatives belonging to the second category TVN.</p