Simeon F. Kouam

Xanthones and oxepino[2, 3-b]chromones from three endophytic fungi.

Three new metabolites, microsphaeropsones A-C (1-3) with a unique oxepino[2,3-b]chromen-6-one (ring-enlarged xanthone) skeleton, were isolated from the endophytic fungus Microsphaeropsis species, co-occurring with their putative biogenetic anthraquinoide precursors citreorosein (4) and emodin (5). From another Microsphaeropsis species, large amounts of fusidienol A (8 a), smaller amounts of emodin (5), the known aromatic xanthones 9 a and 9 b, the new 3,4-dihydrofusidienol A (8 b), and the new aromatic xanthone 9 c were isolated. The endophyte Seimatosporium species produced a new aromatic xanthone, seimatoxanthone A (10), and 3,4-dihydroglobosuxanthone A (12), closely related to alpha-diversolonic ester (13) from Microdiplodia sp.. The structures were determined mainly by extensive 1D and 2D NMR experiments and supported by X-ray single-crystal analysis of 1 and the oxidation product 7. The absolute configurations of the microsphaeropsones A-C (1-3) were established by comparison of the electronic and vibrational circular dichroism (ECD and VCD) spectra of 1 with time-dependent DFT (TDDFT) and DFT calculations by using either the solid-state structures or DFT-optimized geometries as inputs. Preliminary studies indicated that 1, 2, and enone 7 showed antibacterial, fungicidal, and algicidal properties.

Prenylated flavonoids from the aerial parts of Dorstenia mannii

Four new prenylated flavanones, dorsmanins 1, J and epi-dorsmanins F, G, identified, respectively, as 6,7-(2,2-dimethylpyrano)-8-prenyl-5,3,4-trihydroxyflavanone, 6,7-(2,2-dimethyldihydropyrano)-8-prenyl-5,3,4-trihydroxflavanone, and 2-epimers of dorsmanins F and G were isolated from the aerial parts of Dorstenia mannii together with 13 known flavonoids: 4-hydroxylonchocarpin, 4-methoxylonchocarpin, 6-prenylchrysoeriol, 6,8-diprenyleriodictyol, gancaonin P and dorsmanins A-H. The structures of these secondary metabolites were determined by spectroscopic means and by comparison with published data and with authentic specimens for some of the known compounds.

Minor secondary metabolic products from the stem bark of Plumeria rubra Linn. displaying antimicrobial activities.

Four new iridoids viz., plumeridoids A, B, and C and epiplumeridoid C were isolated from the stem bark of Plumeria rubra Linn. together with twenty-four known compounds viz., 1-( P-hydroxyphenyl)propan-1-one, isoplumericin, plumericin, dihydroplumericin, allamcin, fulvoplumerin, allamandin, plumieride, P- E-coumaric acid, 2,6-dimethoxy- P-benzoquinone, scopoletin, cycloart-25-en-3 beta,24-diol, 2,4,6-trimethoxyaniline, ajunolic acid, ursolic acid, oleanolic acid, beta-amyrin acetate, betulinic acid, lupeol and its acetate, 2,3-dihydroxypropyl octacosanoate, glucoside of beta-sitosterol, and a mixture of common sterols (stigmasterol and beta-sitosterol). Their structures were determined by means of spectroscopic data including HREIMS, 1H NMR, 13C NMR, 2D NMR (HMQC, HMBC, NOESY) and by comparison with published data. All but one of thirteen tested compounds exhibited antifungal, antialgal, and/or antibacterial activities.

Antimicrobial prenylated dihydrochalcones from Eriosema glomerata.

Two new natural dihydrochalcones exhibiting antimicrobial properties together with six known compounds were isolated from the Cameroonian medicinal plant Eriosema glomerata. The structures of the new dihydrochalcones were elucidated as 2,4-dihydroxy-4-methoxy-3-( gamma, gamma-dimethylallyl)dihydrochalcone and 2,4-dihydroxy-3-( gamma, gamma-dimethylallyl)dihydrochalcone by detailed spectroscopic analysis. The two new dihydrochalcones, named erioschalcones A ( 1) and B ( 2), demonstrated significant inhibitory activity against the microbial strains Bacillus megaterium, Escherichia coli, Chlorella fusca and Microbotryum violaceum.

Cameroonemide A: a new ceramide from Helichrysum cameroonense

From the extracts of all parts of the plant Helichrysum cameroonense, five compounds were isolated and identified. One of them, a ceramide, named cameroonemide A (1), is reported for the first time as a new natural product. Its structure was determined by comprehensive analyses of their 1D and 2D NMR and HR-EI-MS spectral data. The remaining four known compounds were identified by comparing their spectroscopic data with those reported in the literature as kaurenoic acid (2), 3-acetyloxykaurenoic acid (3), β-sitosterol (4), and β-sitosterol glucopyranoside (5). Preliminary studies showed that 3-acetyloxykaurenoic acid (3) inhibited the alga Chlorella fusca, while kaurenoic acid (2) showed strong antibacterial activity against Bacillus megaterium.

Antiplasmodial activities of furoquinoline alkaloids from Teclea afzelii.

The study of the chemical constituents of the stem bark of Teclea afzelii (Rutaceae) has resulted in the isolation and characterization of four furoquinoline alkaloids, namely kokusaginine (1), tecleaverdoornine (2), maculine (3) and montrifoline (4) together with lupeol (5) and b‐sitosterol glucopyranoside (6). The structures of the isolated compounds were elucidated based on spectroscopic studies. The antimalarial activity of compounds 1–4 against Plasmodium falciparum in vitro shows partial suppression of parasitic growth. Copyright

Tramadol—A True Natural Product?

We have independently investigated the source of tramadol, a synthetic analgesic largely used for treating moderate to severe pain in humans, recently found in the roots of the Cameroonian medicinal plant, Nauclea latifolia. We found tramadol and its three major mammalian metabolites (O-desmethyltramadol, N-desmethyltramadol, and 4-hydroxycyclohexyltramadol) in the roots of N. latifolia and five other plant species, and also in soil and local water bodies only in the Far North region of Cameroon. The off-label administration of tramadol to cattle in this region leads to cross-contamination of the soil and water through feces and urine containing parent tramadol as well as tramadol metabolites produced in the animals. These compounds can then be absorbed by the plant roots and also leached into the local water supplies. The presence of tramadol in roots is, thus, due to an anthropogenic contamination with the synthetic compound.

Sapelenins G-J, acyclic triterpenoids with strong anti-inflammatory activities from the bark of the Cameroonian medicinal plant Entandrophragma cylindricum.

Four acyclic triterpene derivatives named sapelenins G-J (1-4), along with eight known compounds, sapelenins A-D, ekeberin D2 (5), (+)-catechin and epicatechin, and anderolide G, were isolated from the stem bark of the Cameroonian medicinal plant, Entandrophragma cylindricum Sprague, on the basis of bioassay-guided fractionation. Their structures were determined by means of high-resolution mass spectrometry and NMR spectroscopic data, as well as by comparison with the literature values of their analogs. The absolute configurations of the compounds (1-4) were assigned by the modified Moshers method in conjunction with NOESY experiments and chemical modifications. The anti-inflammatory activities of the sapelenins were evaluated by assessing their ability to suppress or inhibit the secretion of cytokine interleukin-17 (IL-17) by human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA). The cytotoxicity of these compounds on PMBCs was further assessed for correctly interpreting their anti-inflammatory responses. The tested compounds demonstrated moderate to significant anti-inflammatory activities by suppressing the secretion of IL-17 by PHA-stimulated human PBMCs. One of them, sapelenin G (1), showed high potency in suppressing the secretion of IL-17 by PBMCs comparable to reference cyclosporine A, without causing any cytotoxic effects (negligible), and deserves further considerations towards developing an effective anti-inflammatory drug.

Analgesic and antiinflammatory activities of the ethyl acetate fraction of Bidens pilosa (Asteraceae).

Bidens pilosa is an Asteraceae widely used in traditional medicine for the treatment of various ailments including pain and inflammation. The present work was undertaken to assess the analgesic and antiinflammatory properties of the ethyl acetate fraction of methylene chloride/methanol (1:1) extract of leaves of Bidens pilosa at the gradual doses of 50, 100 and 200xa0mg/kg in mice and rats, respectively. The analgesic properties of Bidenspilosa were investigated using the acetic acid writhing, hot plate, capsaicin and formalin-induced pain models. This was followed by a study of the antiinflammatory properties using carrageenan, dextran, histamine and serotonin to induce acute inflammation in rat hind paw. The extract provided a significant (pxa0<xa00.01) reduction in pain induced by all four models of nociception. It also presented significant (pxa0<xa00.05) antiinflammatory activity in all four models of acute inflammation. These results show that the ethyl acetate fraction of methylene chloride/methanol (1:1) of Bidens pilosa has both analgesic and antiinflammatory properties. The qualitative analysis of the fraction by the high-performance liquid chromatography (HPLC) fingerprint revealed the presence of two flavonoids, namely quercetin and iso-okanin, known to have antiinflammatory and antinociceptive properties, which could be responsible for the analgesic and antiinflammatory effects observed.

Antiplasmodial and cytotoxic dibenzofurans from Preussia sp. harboured in Enantia chlorantha Oliv.

Two unusual dibenzofurans, preussiafurans A-B (1-2), together with six known compounds have been isolated from the fungus Preussia sp. occurring in Enantia chlorantha Oliv. The structures were established on the basis of 1D and 2D NMR spectroscopy and MS analysis. Compounds 1-4 showed antiplasmodial activity against erythrocytic stages of chloroquine-resistant Plasmodium falciparum (NF54) and moderate cytotoxicity on L6 cell lines with IC50 values of 8.67 and 14.8 μM, respectively.