Polymethoxyflavones from Gardenia oudiepe and semi-synthetic derivatives reduce nociception in mice: Evidence for the involvement of the MAPK pathway.

This study explores the potential of polymethoxyflavones (PMFs) and polyacetylated flavones (PAFs) as novel analgesic and anti-inflammatory agents. Eight derivatives, isolated from Gardenia oudiepe bud exudate or semi-synthesized from commercial kaempferol, underwent evaluations in various in vivo, in vitro, and in silico models. Acetic acid-, formalin-induced pain, and hot-plate tests were conducted in mice (n = 6).

Xanthone Inhibitors of Unfolded Protein Response Isolated from .

The unfolded protein response (UPR) is a key component of fungal virulence. The prenylated xanthone γ-mangostin isolated from (Clusiaceae) fruit pericarp, has recently been described to inhibit this fungal adaptative pathway. Considering that (Calophyllaceae) is known for its high prenylated xanthone content, its stem bark extract was fractionated using a bioassay-guided procedure based on the cell-based anti-UPR assay.

Structure elucidation of an aspidofractinine-type monoterpene indole alkaloid from .

The structure and complete NMR assignments of aspidoreticulofractine, an aspidofractinine -oxide, are reported. Its structure was elucidated based on a combination of spectroscopic techniques including 1D and 2D NMR, high-resolution mass spectrometry, and electronic circular dichroism.

In vitro evaluation of NA1-115-7-loaded nanoemulsions, an MCL-1-specific inhibitor of natural origin, intended to treat B-cell lymphoproliferative disorders after oral administration.

MCL-1, an anti-apoptotic member of the BCL-2 protein family, is overexpressed in many types of cancer and contributes to chemotherapy resistance. The drimane derivative NA1-115-7 is a natural compound isolated from Zygogynum pancheri that can be considered as a very promising lead for treating MCL-1-dependent hematological malignancies. As this drug suffers from low stability in acidic conditions and poor aqueous solubility, we evaluated the potential oral use of NA1-115-7 by encapsulating it in lipid nanoemulsions (NA-NEs) prepared by spontaneous emulsification.

NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes.

The overexpression of antiapoptotic members (BCL-2, BCL-xL, MCL-1, etc.) of the BCL-2 family contributes to tumor development and resistance to chemotherapy or radiotherapy. Synthetic inhibitors targeting these proteins have been developed, and some hematological malignancies are now widely treated with a BCL-2 inhibitor (venetoclax).

Drimane Derivatives as the First Examples of Covalent BH3 Mimetics that Target MCL-1.

Drimane sesquiterpenoid dialdehydes are natural compounds with antiproliferative properties. Nevertheless, their mode of action has not yet been discovered. Herein, we demonstrate that various drimanes are potent inhibitors of MCL-1 and BCL-xL, two proteins of the BCL-2 family that are overexpressed in various cancers, including lymphoid malignancies.

A method to assess algicidal activity of microalgal extracts coupling microalgae produced in stirred closed photobioreactor operating in continuous with pulse amplitude modulated (PAM) fluorometry.

We describe in the present study a quick and reliable method based on chlorophyll a fluorescence to assess putative algicidal effect of different microalgal extracts. We couple microalgal production under chemostat cultivation mode to continuously produce a given microalgae species (e.g.

CANPA: Computer-Assisted Natural Products Anticipation.

Traditional natural products discovery workflows implying a combination of different targeting strategies, including structure- and/or bioactivity-based approaches, afford no information about new compound structures until late in the discovery pipeline. By integrating a MS/MS prediction module and a collaborative library of (bio)chemical transformations, we have developed a new platform, coined MetWork, that is capable of anticipating the structural identity of metabolites starting from any identified compound. In our quest to discover new monoterpene indole alkaloids, we demonstrate the utility of the MetWork platform by anticipating the structures of five previously undescribed sarpagine-like -oxide alkaloids that have been targeted and isolated from the leaves of using a molecular networking-based dereplication strategy fueled by computer-generated annotations.

Natural Inhibitors of the RhoA-p115 Complex from the Bark of Meiogyne baillonii.

In an effort to find potent natural inhibitors of RhoA and p115 signaling G-proteins, a systematic in vitro evaluation using enzymatic and plasmonic resonance assays was undertaken on 11 317 plant extracts. The screening procedure led to the selection of the New Caledonian endemic species Meiogyne baillonii for a chemical investigation. Using a bioguided isolation procedure, three enediyne-γ-butyrolactones (1-3) and two enediyne-γ-butenolides (4 and 5), named sapranthins H-L, respectively, two enediyne carboxylic acid (6 and 7), two depsidones, stictic acid (8) and baillonic acid (9), aristolactams AIa and AIIa (10 and 11), and two aporphines, dehydroroemerine (12) and noraristolodione (13), were isolated from the ethyl acetate extract of the bark.

(+)- and (-)-Ecarlottones, Uncommon Chalconoids from Fissistigma latifolium with Pro-Apoptotic Activity.

Four new compounds, (+)- and (-)-ecarlottone (1), (±)-fislatifolione (5), (±)-isofislatifolione (6), and (±)-fislatifolic acid (7), and the known desmethoxyyangonin (2), didymocarpin-A (3), and dehydrodidymocarpin-A (4) were isolated from the stem bark of Fissistigma latifolium, by means of bioassay-guided purification using an in vitro affinity displacement assay based on the modulation of Bcl-xL/Bak and Mcl-1/Bid interactions. The structures of the new compounds were elucidated by NMR spectroscopic data analysis, and the absolute configurations of compounds (+)-1 and (-)-1 were assigned by comparison of experimental and computed ECD spectra. (-)-Ecarlottone 1 exhibited a potent antagonistic activity on both protein-protein associations with K values of 4.

Dual Beam Depth Profiling and Imaging with Argon and Bismuth Clusters of Prenylated Stilbenes on Glandular Trichomes of Macaranga vedeliana.

Using a time-of-flight secondary ion mass spectrometer equipped with an argon cluster ion for sputtering and a bismuth liquid metal ion source for analysis, both surfaces of leaves and fruits of Macaranga vedeliana, an endemic New Caledonian species, have been for the first time analyzed by a dual beam depth profiling. To prevent in-vacuum evaporation of the liquid content of the small glandular trichomes covering fruits and leaves surfaces and also to be able to analyze their liquid content while preventing any sublimation of the latter, the samples were kept frozen during the whole experiment using a nitrogen cooled sample holder. Thus, it was possible to demonstrate that vedelianin, an active metabolite of the family of prenylated stilbenes named schweinfurthins, is only located in these glandular trichomes.

Unified biomimetic assembly of voacalgine A and bipleiophylline via divergent oxidative couplings.

Bipleiophylline is a highly complex monoterpene indole alkaloid composed of two pleiocarpamine units anchored on an aromatic spacer platform. The synthesis of bipleiophylline is considered as a mountain to climb by the organic chemistry community. Here, a unified oxidative coupling protocol between indole derivatives and 2,3-dihydroxybenzoic acid, mediated by silver oxide, has been developed to produce the core of bipleiophylline.

Fast & easy preparation of 3D scaffolds from methyl benzoate by a diversity oriented synthesis strategy based on Diels-Alder and ene-reactions.

Thermic dimerization of methyl 1,3-cyclohexadiene 2-carboxylate gave original 3D-shape compounds by Diels-Alder cycloaddition and original [6 + 4]-ene reaction. Further selective modifications on an endo [4 + 2] cycloadduct via a diversity oriented synthesis (DOS) strategy quickly led to the preparation of a small library of original 3D scaffolds, providing access to a larger and unexplored chemical space for drug discovery processes.

A New Polycyclic Polyprenylated Acylphloroglucinol Derivative from Garcinia verrucosa.

In our continuing phytochemical screening program aimed at finding major constituents. of endemic Madagascar plants as potential templates for semisynthesis, we investigated the ethyl acetate extract of stem bark of Garcinia verrucosa. Fractionation of the extract led to the isolation of the major compound named garcicosin.

Anacardic Acids from Knema hookeriana as Modulators of Bcl-xL/Bak and Mcl-1/Bid Interactions.

Proteins of the Bcl-2 family are key targets in anticancer drug discovery. Disrupting the interaction between anti- and pro-apoptotic members of this protein family was the approach chosen in this study to restore apoptosis. Thus, a biological screening on the modulation of the Bcl-xL/Bak and Mcl-1/Bid interactions permitted the selection of Knema hookeriana for further phytochemical investigations.

Triterpenes from the exudate of Gardenia urvillei.

A cycloartane gardurvilleic acid, three 3,4-seco-cycloartanes securvienol, secodienurvilleic acid, securvitriol, a 3,4;9,10-seco-cycloartane gardheptlactone, two dammaranes urvilone, urvilol, along with eight known cycloartanes and 3,4-seco-cycloartanes and four known dammaranes have been isolated from the bud exudate of Gardenia urvillei, an endemic tree to the New Caledonian dry forest. Two other dammarane derivatives have been obtained by semisynthesis. The structures of the original compounds were determined by spectroscopic methods and chemical correlations.

Advanced Structural Determination of Diterpene Esters Using Molecular Modeling and NMR Spectroscopy.

Three new jatrophane esters (1-3) were isolated from Euphorbia amygdaloides ssp. semiperfoliata, including an unprecedented macrocyclic jatrophane ester bearing a hemiketal substructure, named jatrohemiketal (3). The chemical structures of compounds 1-3 and their relative configurations were determined by spectroscopic analysis.

LC-MS²-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity.

Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent and selective antiviral activity on the replication of Chikungunya virus (CHIKV) in cell culture. With the objective to found new compounds with anti-CHIKV activities, 45 extracts from various plant parts of 11 Mediterranean Euphorbia and one Mercurialis species were evaluated for selective inhibition of CHIKV replication. All EtOAc extracts, especially those prepared from latex, exhibited significant and selective antiviral activity in a Chikungunya virus-cell-based assay.

Antivascular and anti-parasite activities of natural and hemisynthetic flavonoids from New Caledonian Gardenia species (Rubiaceae).

A series of 16 flavonoids were isolated and prepared from bud exudate of Gardenia urvillei and Gardenia oudiepe, endemic to New Caledonia. Most of them are rare polymethoxylated flavones. Some of these compounds showed noticeable activity against Leishmania (Leishmania) amazonensis, Plasmodium falciparum and Trypanosoma brucei gambiense, in addition to tubulin polymerization inhibition at low micromolar concentration.

Antiplasmodial compounds from the stem bark of Neoboutonia macrocalyx pax.

Ethnopharmacological Relevance: The plant Neoboutonia macrocalyx has been reported in traditional medicine to be used in the treatment of malaria.

Aim Of The Study: To study the in vitro antiplasmodial activity of compounds from the stem bark of Neoboutonia macrocalyx.

Materials And Methods: Compounds were extracted and purified from stem bark of Neoboutonia macrocalyx and their structure identified and confirmed by spectroscopic methods.

Triterpenoid glycosides from the leaves of Meliosma henryi.

Seven triterpenoid glycosides, named meliosmosides A-G, were isolated from the leaves of Meliosma henryi Diels (Sabiaceae). Their structures were elucidated by different spectroscopic methods including 1D and 2D NMR experiments as well as HRESIMS analysis. Isolated compounds were evaluated for their cytotoxic activity against KB cell line.

Pro-apoptotic meiogynin A derivatives that target Bcl-xL and Mcl-1.

The biological evaluation of a natural sesquiterpene dimer meiogynin A 1, is described as well as that of five non-natural analogues. Although active on a micromolar range on the inhibition of Bcl-xL/Bak and Mcl-1/Bid interaction, meiogynin A 1 is not cytotoxic on three cell lines that overexpress Bcl-xL and Mcl-1. Contrarily, one of its analogues 6 with an inverted configuration on the side chain and an aromatic moiety replacing the cyclohexane ring was active on both target proteins, cytotoxic on a micromolar range and was found to induce apoptosis through a classical pathway.

Antioxidant and α-amylase inhibitory activities of extract and isolates from Zygogynum pancheri subsp. arrhantum.

One new sesquiterpenoid (5R(*),8R(*),9R(*),10R(*))-cinnamolide (8), and seven known compounds, 5-hydroxy-7-methoxyflavonone (1), 8-hydroxy-3-(4'-hydroxyphenyl)-6,7-(2″,2″-dimethylchromene)-tetralone (2), 8-hydroxy-3-(3',4'-dihydroxyphenyl)-6,7-(2″,2″-dimethylchromene)-tetralone (3), 1β-E-O-p-methoxycinnamoyl-bemadienolide (4), 1β-O-(E-cinnamoyl)-6α-hydroxy-9-epi-polygodial (5), 1β-O-(E-cinnamoyl)-6α-hydroxypolygodial (6), and 1β-O-E-cinnamoylpolygodial (7) were isolated from the ethyl acetate extract of barks of Zygogynum pancheri subsp. arrhantum (Winteraceae). The structures of these molecules were assigned predominantly based on spectral data.

Jatrophane diterpenes as inhibitors of chikungunya virus replication: structure-activity relationship and discovery of a potent lead.

Bioassay-guided purification of an EtOAc extract of the whole plant of Euphorbia amygdaloides ssp. semiperfoliata using a chikungunya virus-cell-based assay led to the isolation of six new (1-4, 9, and 10) and six known (5-7, 8, 11, and 12) jatrophane esters. Their planar structures and relative configurations were determined by extensive spectroscopic analysis, and their absolute configurations by X-ray analysis.