Cyril Antheaume

On the Benefits of Rubbing Salt in the Cut: Self‐Healing of Saloplastic PAA/PAH Compact Polyelectrolyte Complexes

The inherent room temperature mending and self-healing properties of saloplastic PAA/PAH CoPECs are studied. After ultracentrifugation of PAA/PAH polyelectrolyte complexes, tough, elastic materials are obtained that undergo self-healing facilitated by salt. At intermediate salt concentrations the CoPECs remain elastic enough to recover their original shape while the chains are mobile enough to repair the cut, thus leading to actual self-healing behavior.

Theoretical mechanistic study of the TBD-catalyzed intramolecular aldol reaction of ketoaldehydes.

The intramolecular aldol reaction of acyclic ketoaldehydes catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is investigated using density functional theory calculations. Compared to the proline-catalyzed aldol reaction, the use of TBD provides a unique and unusual complete switch of product selectivity. Three mechanistic pathways are proposed and evaluated. The calculations provide new insights into the activation mode of bifunctional guanidine catalysts. In the favored mechanism, TBD first catalyzes the enolization of the substrate and then the C-C bond formation through two concerted proton transfers. In addition, the computationally predicted stereochemical outcome of the reaction is in agreement with the experimental findings.

Antioxidant Biomarkers from Vanda coerulea Stems Reduce Irradiated HaCaT PGE-2 Production as a Result of COX-2 Inhibition

Background In our investigations towards the isolation of potentially biologically active constituents from Orchidaceae, we carried out phytochemical and biological analyses of Vanda species. A preliminary biological screening revealed that Vanda coerulea (Griff. ex. Lindl) crude hydro-alcoholic stem extract displayed the best DPPH /•OH radical scavenging activity and in vitro inhibition of type 2 prostaglandin (PGE-2) release from UVB (60 mJ/cm2) irradiated HaCaT keratinocytes. Principal Findings Bio-guided fractionation and phytochemical analysis led to the isolation of five stilbenoids: imbricatin (1) methoxycoelonin (2) gigantol (3) flavidin (4) and coelonin (5). Stilbenoids (1–3) were the most concentrated in crude hydro-alcoholic stem extract and were considered as Vanda coerulea stem biomarkers. Dihydro-phenanthropyran (1) and dihydro-phenanthrene (2) displayed the best DPPH/•OH radical scavenging activities as well as HaCaT intracellular antioxidant properties (using DCFH-DA probe: IC50 8.8 µM and 9.4 µM, respectively) compared to bibenzyle (3) (IC50 20.6 µM). In turn, the latter showed a constant inhibition of PGE-2 production, stronger than stilbenoids (1) and (2) (IC50 12.2 µM and 19.3 µM, respectively). Western blot analysis revealed that stilbenoids (1–3) inhibited COX-2 expression at 23 µM. Interestingly, stilbenoids (1) and (2) but not (3) were able to inhibit human recombinant COX-2 activity. Conclusions Major antioxidant stilbenoids (1–3) from Vanda coerulea stems displayed an inhibition of UVB-induced COX-2 expression. Imbricatin (1) and methoxycoelonin (2) were also able to inhibit COX-2 activity in a concentration-dependent manner thereby reducing PGE-2 production from irradiated HaCaT cells. Our studies suggest that stilbenoids (1–3) could be potentially used for skin protection against the damage caused by UVB exposure.

Direct Guanidinylation of Aryl and Heteroaryl Halides via Copper-Catalyzed Cross-Coupling Reaction

A modified Ullmann reaction using p-methoxybenzyl (PMB) guanidine as guanidinylation agent yielded various aryl and heteroaryl guanidines in good yields.

Glucosyloxybenzyl Eucomate Derivatives from Vanda teres Stimulate HaCaT Cytochrome c Oxidase.

Eucomic acid [(2R)-2-(p-hydroxybenzyl)malic acid)] (1) and three new glucopyranosyloxybenzyl eucomate derivatives, vandaterosides I (2), II (3), and III (4), were isolated and identified from the stems of Vanda teres. Their cellular antiaging properties were evaluated in a human immortalized keratinocyte cell line (HaCaT) by monitoring their effect on cytochrome c oxidase activity, implicated in mitochondrial respiratory function and cellular energy production. Eucomic acid (1) and vandateroside II (3) increased cytochrome c oxidase activity and/or expression, without enhancing cellular mitochondrial content. These two V. teres biomarkers apparently contributed to stimulate respiratory functions in keratinocytes. Since aging and its pathologies may be ascribed to a decline in mitochondrial functions, these biomarkers have the potential to become new natural ingredients for antiaging preparations to remedy age-related disorders such as skin aging.

Triterpenoid saponins from Albizia lebbeck (L.) Benth and their inhibitory effect on the survival of high grade human brain tumor cells.

As part of our search of new bioactive triterpenoid saponins from Cameroonian Mimosaceae plants, phytochemical investigation of the roots of Albizia lebbeck led to the isolation of two new oleanane-type saponins, named lebbeckosides A-B (1-2). Their structures were established on the basis of extensive 1D and 2D NMR ((1)H, (13)C NMR, DEPT, COSY, TOCSY, ROESY, HSQC, and HMBC) and HRESIMS studies, and by chemical evidence. Compounds 1-2 were evaluated for their inhibitory effect on the metabolism of high grade human brain tumor cells, the human glioblastoma U-87 MG cell lines and the glioblastoma stem-like TG1 cells isolated from a patient tumor, and known to be particularly resistant to standard therapies. The isolated saponins showed significant cytotoxic activity against U-87 MG and TG1 cancer cells with IC50 values of 3.46 μM and 1.36 μM for 1, and 2.10 μM and 2.24 μM for 2, respectively.

Antiplasmodial sesquiterpenes from the seeds of Salacia longipes var. camerunensis

Phytochemical investigation of the seeds of Salacia longipes var. camerunensis led to the isolation of four sesquiterpenoid derivatives, salaterpene A (1) (1α,2β,8β-triacetoxy-6β,9β-dibenzoyloxy-4β-hydroxy-dihydro-β-agarofuran), salaterpene B (2) (1α,2β,8β-triacetoxy-9β-benzoyloxy-6β-cinnamoyloxy-4β-hydroxy-dihydro-β-agarofuran), salaterpene C (3) (1α,2β-diacetoxy-6β,9β-dibenzoyloxy-4β-hydroxy-dihydro-β-agarofuran) and salaterpene D (4) (2β-acetoxy-1α,6β-dibenzoyloxy-4β-hydroxy-9β-nicotinoyloxy-dihydro-β-agarofuran) together with two known compounds (5 and 6). The structures of the compounds were established by means of NMR spectroscopy. Compounds 1-4 and 6 were tested in vitro for their antiplasmodial activity against Plasmodium falciparum chloroquine-resistant strain W2. All the tested compounds exhibited a moderate potency with IC50 below 2.7 μM.

Isolation and characterisation of the monoterpenoid indole alkaloids of Aspidosperma pyrifolium

Malaria is a major parasitic infection in many tropical and subtropical regions with the most severe forms of the disease being caused by Plasmodium falciparum. Dramatic increases in the resistance of this mosquito-transmitted parasite to classical treatments have been observed in recent years, and much research effort is now aimed at the discovery of novel natural products with antiplasmodial activities. On the basis of its use in popular medicine, Aspidosperma pyrifolium Mart. (Apocynaceae), a tree popularly known as “pereiro-do-sertão,” was selected for detailed study. A phytochemical investigation of the aqueous extract of its stem bark revealed the presence of two known monoterpenoid indole alkaloids, 15-demethoxypyrifoline and aspidofractinine, together with the novel compound N-formylaspidofractinine. The structures of these compounds were established from UV, IR, MS and NMR data, and their 1H- and 13C-NMR spectra have been unambiguously assigned for the first time.

Antimalarial compounds from the stem bark of Vismia laurentii.

A phytochemical study of the stem bark of Vismia laurentii resulted in the isolation of a tetracyclic triterpene, tirucalla-7,24-dien-3-one (1), and seven other known compounds: 3-geranyloxyemodin (2), vismiaquinone A (3), vismiaquinone B (4), bivismiaquinone (5), epifriedelinol (6), betulinic acid (7) and stigmasta-7,22-dien-3-ol (8). The structure of all these compounds was elucidated by spectroscopic means. The stem bark extract and compounds 1 and 3 showed good antimalarial activity against the W2 strain of Plasmodium falciparum.

Phenotype-specific apoptosis induced by three new triterpenoid saponins from Albizia glaberrima (Schumach. & Thonn.) Benth.

As part of our search of new bioactive saponins from Cameroonian medicinal plants, phytochemical investigation of the roots of Albizia glaberrima led to the isolation of three new oleanane-type saponins, named glaberrimosides A-C (1-3). Their structures were established by direct interpretation of their spectral data, mainly HRESIMS, 1D NMR (1H, 13C NMR, and DEPT) and 2D NMR (COSY, ROESY, HSQC and HMBC) as 3-O-[α-L-arabinopyranosyl-(1 → 6)-[β-D-glucopyranosyl-(1 → 2)]-β-D-glucopyranosyl]-28-O-[β-D-glucopyranosyl-(1 → 6)-[β-d-glucopyranosyl-(1 → 2)]-β-D-glucopyranosyl]-oleanolic acid (1), 3-O-[α-L-arabinopyranosyl-(1 → 6)-[β-D-glucopyranosyl-(1 → 2)]-β-D-glucopyranosyl]-28-O-[β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl]-oleanolic acid (2), and 3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]-28-O-[β-D-glucopyranosyl-(1 → 6)-[β-D-fucopyranosyl-(1 → 2)]-β-D-glucopyranosyl]-oleanolic acid (3). The pro-apoptotic effect of the three saponins was evaluated on three human cell lines (pancreatic carcinoma AsPC-1, hematopoietic monocytic THP-1, and human fibroblast cell line BJ). Saponins 1-3 specifically induced apoptosis of pancreatic carcinoma cell (AsPC-1) in a dose-dependent manner. More interestingly, there were inactive on monocytic (THP-1) and normal human fibroblast (BJ) cell lines.