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 IC₅₀ value of 0.022 μM, while compound <b>2</b> had weaker cytotoxicity, with an IC₅₀ value of 1.4 μM. When tested against other cancer cell lines (MCF-7, MCF-7R, and HT29), <b>1</b> showed an IC₅₀ of 0.014 against MCF-7R cells and an IC₅₀ 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 IC₅₀ value of 0.022 μM, while compound <b>2</b> had weaker cytotoxicity, with an IC₅₀ value of 1.4 μM. When tested against other cancer cell lines (MCF-7, MCF-7R, and HT29), <b>1</b> showed an IC₅₀ of 0.014 against MCF-7R cells and an IC₅₀ 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 (IC₅₀ 9 μM). Cytotoxic evaluation against KB cells showed that compound <b>7</b> had an IC₅₀ of 4 μM, followed by <b>11</b> (IC₅₀ 10 μM) and <b>3</b> (IC₅₀ 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 IC₅₀ 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 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

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 ¹H and ¹H–¹³C 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>_i = 19.2, 12.6, and 19.4 μM, respectively) and Mcl-1 (<i>K</i>_i = 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>_i = 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