Antibacterial activity of some natural products against bacteria expressing a multidrug-resistant phenotype.

The present study assessed the antimicrobial activities of various natural products belonging to the terpenoids, alkaloids and phenolics against a collection of Gram-negative multidrug-resistant (MDR) bacteria. The results demonstrated that most of the compounds were extruded by bacterial efflux pumps. In the presence of the efflux pump inhibitor phenylalanine arginine ß-naphthylamide (PAßN), the activities of laurentixanthone B (xanthone), plumbagin (naphthoquinone), 4-hydroxylonchocarpin (flavonoid) and MAB3 (coumarin) increased significantly against all studied MDR bacteria. Laurentixanthone B, 4-hydroxylonchocarpin and MAB3 contained the same pharmacophoric moiety as plumbagin. This study indicates that the AcrAB-TolC (Enterobacteriaceae) and MexAB-OprM (Pseudomonas aeruginosa) efflux pumps are involved in resistance of Gram-negative bacteria to most of the natural products.

Food preservative potential of essential oils and fractions from Cymbopogon citratus, Ocimum gratissimum and Thymus vulgaris against mycotoxigenic fungi.

The food preservative potential of essential oils from three aromatic plants Cymbopogon citratus, Ocimum gratissimum and Thymus vulgaris and their fractions was investigated against two mycotoxigenic strains each of Aspergillus ochraceus, Penicillium expansum and P. verrucosum. The fungicidal activity was determined and expressed as a Number of Decimal Reduction of the colony forming units per ml (NDR cfu). The influence of pH variation on this activity was studied. The NDR cfu varied with the essential oils and its concentration, the pH of the medium and the strain tested. The essential oils from O. gratissimum exhibited the highest activity against the six fungal strains under the three pH tested. T. vulgaris and C. citratus essential oils were less active against the Penicillium species tested and A. ochraceus, respectively. Potassium sorbate did not present any activity at pH 6 and 9. At pH 3, its NDR cfu was the lowest against the six fungal strains. At the same pH and at 4000 ppm, the three essential oils presented a NRD cfu > or = 6 against strains of A. ochraceus and P. expansum. The same result was obtained with T. vulgaris and C. citratus at 8000 ppm against both strains of P. verrucosum. The highest activity of the three essential oils was recorded at pH 3 against A. ochraceus strains and at pH 9 against both species of Penicillium. From the fractionation, three active fractions were obtained each from C. citratus and O. gratissimum, and two active fractions from T. vulgaris. These active fractions exhibited a NDR cfu, two to seven folds higher than that of the complete essential oils.

Apoptotic effects on B-cell chronic lymphocytic leukemia (B-CLL) cells of heterocyclic compounds isolated from Guttiferaes.

A series of 10 heterocyclic compounds purified from Allanblackia were tested on two B cell lines, ESKOL and EHEB, and on cells from B-CLL patients. Several molecules inhibited the proliferation of both cell lines and promoted apoptosis of B-CLL cells through different mechanisms, some of them elicited a dissipation of the mitochondrial transmembrane potential, other triggered caspase-3 activation and cleavage of the inducible nitric oxide synthase. Blood mononuclear cells and B-lymphocytes from healthy donors appeared less sensitive than B-CLL cells. These results indicate that these molecules may be of interest in the development of new therapies for B-CLL.

Antimicrobial and antileishmanial xanthones from the stem bark of Allanblackia gabonensis (Guttiferae).

The phytochemical study of stem bark of Allanblackia gabonensis has resulted in the isolation and characterisation of one new xanthone derivative, named allanxanthone D, together with 10 known compounds, including 6 xanthones derivatives, allanxanthone A, 1,5-dihydroxyxanthone, 1,7-dihydroxyxanthone and 1,3,6,7-tetrahydroxy-2-(3-methylbut-2-enyl)xanthone, forbexanthone, 6-deoxyisojacareubin, one polyisoprenylated benzophenone, guttiferone F, one flavanol, epicathechin, two phytosterols, beta-sitosterol and campesterol. The structures of these compounds were established on the basis of one- and two-dimensional NMR homo- and hetero-nuclear evidence. These compounds were evaluated for their activity against Leishmania amazonensis in vitro and antimicrobial activities against a range of Gram negative and Gram positive bacteria.

Antimicrobial activity of the methanolic extract and of the chemical constituents isolated from Newbouldia laevis.

The methanolic extract (NLB) and ten compounds isolated from the root bark of Newbouldia laevis Seem, namely chrysoeriol (1), newbouldiaquinone (2), 2-acetylfuro-1,4-naphthoquinone (3), 2-hydroxy-3-methoxy-9,10-dioxo-9,10-dihydroanthracene-1-carbaldehyde (4), lapachol (5), beta-sitosterol-3-O-beta-D-glucopyranoside (6), oleanolic acid (7), canthic acid (8) newbouldiamide (9) and 2-(4-hydroxyphenyl)-ethyltrioctanoate (10), were tested for in vitro antimicrobial activity. Twenty one microorganisms belonging to six Gram-positive and twelve Gram-negative bacterial species as well as three yeasts from Candida species were tested for their susceptibility to NLB and the pure isolated compounds based on the Agar Hole Diffusion test and the Liquid Dilution method. The Hole Diffusion assay indicated that NLB and compound 7 were active against all tested pathogens while other compounds showed selective activity with the antimicrobial spectra varying from 76% (compound 10) to 95 % (compound 6). Minimal inhibitory concentrations (MIC) also illustrated the important antimicrobial activity of NLB and of the isolated compounds. MIC values obtained varied from 9.76 to 312.50 microg/ml for NLB, and 0.038 to 9.76 microg/ml for pure compounds against most of the tested microorganisms. The antimicrobial activities of compounds 2, 4 and 9 are described here extensively for the first time. The results indicate a promising basis for the use of Newbouldia laevis and some of its active principles in the treatment of infectious diseases.

Antimalarial and vasorelaxant constituents of the leaves of Allanblackia monticola (Guttiferae).

Phytochemical investigation of the leaves of Allanblackia monticola led to the isolation and characterisation of five prenylated xanthones [1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)xanthone 1, alpha-mangostin 2, tovophyllin A 3, allanxanthone C 4 and 1,7-dihydroxy-3-methoxy-2-(3-methylbut-2-enyl)xanthone 5], two biflavonoid derivatives (amentoflavone 6 and podocarpusflavone A 7) and one pentacyclic triterpene (friedelan-3-one 8). The structures of these compounds were established on the basis of homo- and hetero-nuclear, one- and two-dimensional, nuclear magnetic resonance. Compounds 2-8 and a crude methanolic extract of A. monticola leaves were each tested for antimalarial activity in vitro, using the chloroquine-sensitive F32 and chloroquine-resistant FcM29 strains of Plasmodium falciparum; the median inhibitory concentrations (IC(50)) recorded varied from 0.7 to 83.5 mug/ml. The cytotoxicities of the compounds and crude extract, against cultures of human melanoma cells (A375), were then investigated, and cytotoxicity/antimalarial IC(50) ratios of 0.6-16.75 were recorded. In tests involving aortic rings from guinea pigs, a crude extract of the leaves of A. monticola was found to induce concentration-dependent vasorelaxation, causing up to 82% and 42% inhibition of noradrenaline- and KCl-induced contractions, respectively. The corresponding values for compounds 2 and 6 when tested against noradrenaline-induced contractions were approximately 18% and 35%, respectively.

Vasodilator effect of the extracts and some coumarins from the stem bark of Mammea africana (Guttiferae).

CH(2)Cl(2) fraction obtained from the stem bark of Mammea africana inhibited noradrenaline (NA) or KCl-induced contraction in isolated guinea pig and rat aorta. The vasorelaxant potency of the CH(2)Cl(2) fraction of Mammea africana was diminished by a pre-treatment with Nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, which was however not affected by indomethacin pre-treatment. These findings indicated that the vasorelaxant effect of Mammea africana may be partially endothelium dependent, mediated by nitric oxide and that vasoactive prostanoids might not be contributing to the vasorelaxation effect. Three bioactive compounds were isolated from this CH(2)Cl(2) fraction and identified as 4-n-propylcoumarins (1) (mammea B/BB), 4-phenylcoumarins (2) (mammea A/AA or mammeisin) and (B/BA) (3) and might involved in the vasorelaxant effect of the extract. The mechanisms of the vasorelaxant effect might therefore be multiple, including endothelium dependence and the mechanisms, which interfere with the liberation of Ca(2+) into the muscle cell.

Securidacaxanthone A, a heptaoxygenated xanthone from Securidaca longepedunculata.

From the root bark of Securidaca longepedunculata, a heptaoxygenated xanthone (1) has been isolated as well as two known xanthones (2) and (3) and two salicylic acid derivatives (4) and (5). The structure of 1 has been elucidated from 1H and 13C-NMR spectral data.

Cytotoxic and antimicrobial coumarins from Mammea africana.

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.

In-vivo antimalarial activity of some oxygenated xanthones.

A series of oxygenated xanthones was prepared so that the antimalarial activity of each compound could be evaluated in vivo, using 4-day suppressive assays against Plasmodium berghei ANKA in BALB/c mice. When given in a dose of 20 mg/kg.day for 4 days, most of the compounds produced significant chemosuppression of parasitaemia. The most active compound was 1,3,6,8-tetrahydroxyxanthone, which reduced the percentage of erythrocytes infected by 70.5%, followed by norlichexanthone (44.3%) and its isomer, 1,3,8-trihydroxy-6-methylxanthone (37.0%). Whereas di-C-allyl-dihydroxyxanthone showed lower but still notable activity (33.4%), 1,3-dihydroxyxanthone was much less active (15.1%). This appears to be the first demonstration of the antimalarial activity of some hydroxyxanthones in vivo.

Scaphopetalone and scaphopetalumate, a lignan and a triterpene ester from Scaphopetalum thonneri.

From the methanol extract of the stem bark of Scaphopetalum thonneri, two new compounds, including one lignan, named scaphopetalone, one new ester of ferulic acid, named scaphopetalumate were isolated together with three known compounds including: two coumarins (scopoletin and scopolin), and one pentacyclic triterpene (oleanolic acid). The structure of the new compounds were elucidated by means of spectroscopic analyses.

Cytotoxic isoflavones from Erythrina indica.

Bioassay-directed fractionation of the CH(2)Cl(2)-MeOH (1:1) extract of the stem bark of Erythrina indica, has resulted in the isolation of two new isoflavone derivatives named indicanines D and E together with 11 known compounds including: six isoflavones (genistein, wighteone, alpinumisoflavone, dimethylalpinumisoflavone, 8-prenyl erythrinin C, and erysenegalensein E), one cinnamate (erythrinassinate B), two pentacyclic triterpenes (oleanolic acid and erythrodiol), and two phytosterols (stigmasterol and its 3-O-beta-D-glucopyranoside). The structures of the new compounds were elucidated by means of spectroscopic analysis. The in vitro cytocidal activity against KB cells of some of the isolated compounds is also reported.

Asebotin, a dihydrochalcone glucoside from Guibourtia tessmannii.

Asebotin (1), a dihydrochalcone glucoside, was isolated from the stem bark of Guibourtia tessmanni and characterised by means of spectroscopic analysis including 1H-, 13C, MS and 1D Noe difference experiment.

Diterpenoid and limonoids from the stem of Pterorhachis zenkeri.

One new diterpenoid, methyl 3alpha-hydroxy-7-oxo-dehydroabietate (1), two new limonoids, 3alpha-deacetyl-amoorastatin (2) and 9beta-amoorastatin (3), and the known limonoid amoorastatin (4) were isolated from the stem of Pterorhachis zenkeri.

Indicanine A, a new 3-phenylcoumarin from root bark of Erythrina indica.

A new 3-phenylcoumarin, indicanine A (1), has been isolated from the root bark of the African medicinal plant Erythrina indica, together with three known compounds, robustic acid (2), daidzein, and 8-prenyldaidzein. The structure of the new compound was characterized, as 4-hydroxy-5-methoxy-3-(4'-methoxyphenyl)-2" -(1-methylethenyl)dihydrofurano[4",5":6,7]coumarin by means of extensive spectroscopic analyses. The compounds were found to be devoid of in vitro antibacterial activity.

Indicanines B and C, two isoflavonoid derivatives from the root bark of Erythrina indica.

In addition to two known compounds, 5,4'-di-O-methylalpinumisoflavone and cajanin, a new 3-phenylcoumarin metabolite, named indicanine B, and a new isoflavone derivative, named indicanine C, were isolated from the root bark of Erythrina indica. By means of spectroscopic analysis, the structures of the new compounds were characterized as 4-hydroxy-3-(4'-hydroxyphenyl)-5-methoxy-2",2"-dimethylpyrano [5",6":6,7] coumarin and 4'-hydroxy-5-methoxy-2",2"-dimethylpyrano [5",6":6,7] isoflavone, respectively. The 13C-NMR data of cajanin and the in vitro antimicrobial spectrum and potencies of the isolated compounds are also reported.

Prenylated isoflavanone from Erythrina eriotricha.

Bioassay-directed fractionation of a methylene chloride extract of the root bark of Erythrina eriotricha resulted in the isolation of a novel isoflavanone, named eriotrichin B, and the five known pterocarpans, isonorautenol, erybraedin A, erybraedin C, erybraedin D and erybraedin E. The structure of the new compound has been investigated by extensive spectroscopic studies, including 2D NMR and chemical evidence. The in vitro antimicrobial spectrum and potencies of the isolated compounds are also reported.

Sigmoidins J and K, two new prenylated isoflavonoids from Erythrina sigmoidea.

In addition to the two known compounds neotautenol [2] and erythrinassinate B [4], two new compounds, an isoflavanone named sigmoidin J [1] and a coumestan derivative named sigmoidin K [3], have been isolated and characterized from the root bark of the Cameroonian medicinal plant Erythrina sigmoidea. Their structures have been established as 7, 4'-dihydroxy-2',5'-dimethoxy-6'(gamma, gamma-dimethylally)isoflavanone [1] and 3,9-dihydroxy-2,10-(gamma, gamma dimethylallyl) coumestan [3], respectively, by spectroscopic techniques and from chemical evidence.

Prenylated isoflavanone from the roots of Erythrina sigmoidea.

A novel prenylated isoflavanone, sigmoidin I, has been isolated from the roots of Erythrina sigmoidea, in addition to the known isoflavones, corylin and neobavaisoflavone and the known pterocarpan, phaseollidin. Its structure was established as 7,4'-dihydroxy-3'-methoxy-5'-(3-methylbut-2-enyl) isoflavanone by means of spectroscopic analyses and chemical transformations. Neobavaisoflavone displayed antifungal potency in vitro with minimum inhibitory concentrations against Aspergillus fumigatus and Cryptococcus neoformans, of 50 mg ml-1.

Auriculatin 4'-O-Glucoside: A New Prenylated Isoflavone Glycoside from Erythrina eriotricha1.

In addition to known compounds, sigmoidin C and 8-(3,3-dimethylallyl)-erythrinin C, also called senegalensin, a new isoflavone glycoside designated auriculatin 4'- O-glucoside was isolated from the chloroform extract of the stem bark of ERYTHRINA ERIOTRICHA. Its structure was elucidated as 7,6-(2''',2'''-dimethyl-2 H-pyrano)-2',5-dihydroxy-8-(3,3-dimethylallyl)-isoflavone 4'- O-beta- D-glucoside on the basis of spectroscopic methods and chemical evidence.