Bernard Bodo

Isocryptolepine from Cryptolepis sanguinolenta

A new alkaloid, 5-methyl, 5H-indolo-[3,2-c]-quinoline named isocryptolepine, has been isolated from the roots of Cryptolepis sanguinolenta and its structure determined from spectroscopic data, including IR, MS and NMR.

Antimalarial Activity of Cryptolepine and Isocryptolepine, Alkaloids Isolated from Cryptolepis sanguinolenta

Cryptolepis sanguinolenta extracts are currently used by African herbalists to cure malaria but the compounds involved in its antimalarial activity have not been identified. Two alkaloids, cryptolepine and isocryptolepine, have been isolated from the roots of C. sanguinolenta and their antimalarial activity evaluated. Both alkaloids possess intrinsic inhibitory activity against the human malaria parasite, Plasmodium falciparum in vitro, whatever the chloroquine‐resistance status of the strains used. Cryptolepine was slightly more efficient for parasite killing with an IC50 in the range of 0.2 to 0.6 μMSC compared with an IC50 of about 0.8 μMSC for isocryptolepine. The antimalarial activity of cryptolepine was confirmed in vivo on the rodent malarial parasites Plasmodium vinckei petteri and Plasmodium berghei ANKA.

Interaction of trichorzianines A and B with model membranes and with the amoeba Dictyostelium

Trichorzianines A (TA) and B (TB) are microheterogeneous mixtures of antibiotic nonadecapeptides of the peptaibol class which interact with lipidic membranes and modify their permeability properties. The TB differ from the TA by replacement of the Gln-18 by a Glu, giving rise to a C-terminal negative charge at neutral pH. The role of this charge on the trichorzianine-lipid interaction was investigated with model membranes by fluorescence spectroscopy and the results were correlated with the biological activity toward the amoeba Dictyostelium discoideum. The interaction of the acidic trichorzianine TB IIIc (Glu-18) with phospholipid bilayers and the subsequent induced permeability were weaker than that exhibited by the uncharged TA IIIc (Gln-18) and MeTB IIIc (TB IIIc monomethyl ester). The unfavourable effect of the negative charge in TB IIIc was strongly enhanced by incorporation of cholesterol in the bilayer. Similarly, TA IIIc as well as MeTB IIIc induced growth inhibition and lysis of the amoeba Dictyostelium at four times lower concentrations than TB IIIc. The results suggested that the interaction of trichorzianines with the phospholipid bilayer and the subsequent modifications of permeability were involved in the inhibitory properties and cell lysis induced by trichorzianines toward Dictyostelium.

Cytotoxic and antimicrobial coumarins from Mammea africana

Abstract Six coumarin derivatives [three 4-phenylcoumarins (Mammea A/AA, Mammea A/BA and MAB 3), two 4-n-propylcoumarins (Mammea B/BB and Mammea B/BA) and one 4-n-pentylcoumarin (Mammea C/OB)], 1,5-dihydroxyxanthone and 1-methoxy-5-hydroxyxanthone have been isolated from the stem bark of Mammea africana Sabine collected in Cameroon. Although known, the structures of the coumarin derivatives were confirmed by spectral analysis, including two-dimensional nuclear magnetic resonance. All the coumarin compounds showed noteworthy cytotoxicity against the human 9-KB cell line. Both of the 4-n-propylcoumarins were also found to exhibit significant activity against Staphylococcus aureus.

Curcacycline B, a cyclic nonapeptide from Jatropha curcas enhancing rotamase activity of cyclophilin

The structure of curcacycline B (1), a cyclic nonapeptide isolated from Jatropha curcas latex was elucidated by combination of chemical degradation, LSIMS data and 2D NMR experiments. Curcacycline B was shown to enhance the rotamase activity of human cyclophilin B.

Structural elucidation of trikoningins KA and KB, peptaibols from Trichoderma koningii

A Trichoderma koningii strain collected in Uruguay produced two antibiotic membrane-active peptidic groups, the trikoningins KA and KB, from which the main components KA V, KB I and KB II were purified. The peptide sequences were elucidated by FAB mass spectrometry and high-field NMR experiments. KA V was a nonadecapeptaibol, whereas KB I and KB II were two 11-residue lipopeptaibols. They all displayed antibiotic activity against Staphylococcus aureus. Their membrane-modifying properties were examined by following the leakage of liposome-entrapped carboxyfluorescein. KA V induced similar permeability modifications to those exhibited by known 19-residue peptaibols, while the KB I and KB II activities were weaker.

Lophirone A, A biflavonoid with unusual skeleton from Lophira lanceolata.

Lophirone A, a new biflavonoid have been isolated from the stem bark of Lophira lanceolata. The structure was elucidated by MS, 2D 1H and 13C NMR including INADEQUATE to determine the carbon framework. It involved an aryl shift from one flavonoid unit to the second.

Membrane permeabilisation and antimycoplasmic activity of the 18-residue peptaibols, trichorzins PA

The membrane permeabilisation properties of six linear natural 18-residue peptaibols, termed trichorzins PA, have been assessed on liposomes and on mollicutes (trivial name, mycoplasmas), a class of parasitic bacteria characterized by a small genome, the lack of a cell wall, a minute cell size, and the incorporation in their plasma membrane of exogenously supplied cholesterol. The trichorzins PA used in this study (PA II, PA IV-VI, PA VIII, and PA IX) differ between them by amino acid or amino alcohol substitutions at positions 4, 7, and 18, and form slightly amphipathic alpha-helices. They proved bactericidal for mollicutes belonging to the genera Acholeplasma, Mycoplasma, and Spiroplasma, with minimal inhibitory concentrations (3.12</=MICs</=50 microM) generally 2 to 4 fold higher than those of alamethicin F50, a related 20-residue peptide (1.56</=MICs</=12.5 microM). Spiroplasma cells were apparently not protected by the presence of spiralin on their surface. The activities of the six trichorzins PA were not influenced by their sequence variations and no synergistic effect was observed. Consistent with the marginal effect of cholesterol on the incorporation of the trichorzins PA into liposome bilayers, the antibiotic activity was independent of the amount of cholesterol in the membranes of the different mollicutes. The trichorzins PA and alamethicin inhibited the motility of Spiroplasma melliferum, the helical cells being deformed and split into coccoid forms. Membrane potential measurements in Acholeplasma laidlawii and S. melliferum showed that trichorzin PA V and alamethicin F50 very efficiently depolarized the plasma membrane of mollicutes. This was consistent with fluorescence and 23Na NMR measurements on liposomes that revealed the permeabilisation of the lipid bilayer and the nonselective ionophoric activity of the trichorzins PA. These data suggest that the bactericidal activity exhibited by the trichorzins PA on mollicutes is due to the permeabilisation of the plasma membrane.

Pohlianins A, B and C, cyclic peptides from the laxes of Jatropha pohliana ssp. molissima

Abstract From the EtOAc extract of the latex of Jatropha pohliana (Euphorbiaceae), two cyclic heptapeptides, pohlianins A (1) and B (2) and one cyclic octapeptide, pohlianin C (3) were isolated by a multi-step chromatography procedure, including HPLC. Their structure were elucidated by chemical degradation, mass spectrometry, homonuclear and heteronuclear NMR experiments. Conformational analysis of these peptides was made by using NMR experiments and distance geometry calculations. Their antimalarial activities were examined.

Pentacyclic triterpenes from Combretum nigricans

Abstract From the bark of Combretum nigricans , four pentacyclic triterpenes have been isolated and their structures elucidated from spectral data as the known arjungenin and arjunglucoside, a new pentacyclic triterpene, combregenin (2α,3β,6β,19α,23-pentahydroxyolean-12-en-28-oic acid) and a new saponin, combreglucoside (β- d -glucopyranosyl 2α,3β,6β,19α,23-pentahydroxyolean-12-en-28-oate).