Habropetaline A,an antimalarial naphthylisoquinoline alkaloid from Triphyophyllum peltatum

The isolation, structural elucidation, and antiprotozoal activities of habropetaline A, a novel naphthylisoquinoline alkaloid from Triphyophyllum peltatum, are described. This alkaloid had previously only been identified on line, by the LC-MS/MS-NMR-CD triad, in the crude extract of the rare and difficult-to-provide related plant species Habropetalum dawei, whose small quantities available had not permitted to isolate the compound. As predicted by quantitative structure-activity relationship (QSAR) investigations, habropetaline A exhibits strong antimalarial activity against Plasmodium falciparum, while it is inactive against other protozoal pathogens (Trypanosoma brucei rhodesience, T. cruzi, and Leishmania donovani).     

Ancistroheynine B and two further 7,3'-coupled naphthylisoquinoline alkaloids from Ancistrocladus heyneanus Wall

A new axially chiral naphthylisoquinoline alkaloid, ancistroheynine B (7), has been isolated from the leaves of the Indian liana Ancistrocladus heyneanus Wall., along with two known related alkaloids, ancistrocladidine (3) and ancistrotanzanine C (6), which are 7,3'-coupled, too. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. Biological activities of ancistroheynine B against the pathogens of malaria, leishmaniasis, Chagas' disease, and African sleeping sickness were evaluated.     

Ancistrolikokine D,a 5,8'-coupled naphthylisoquinoline alkaloid,and related natural products from Ancistrocladus likoko

A new naphthylisoquinoline alkaloid, ancistrolikokine D, and the likewise 5,8'-coupled alkaloid ancistroealaine A, as well as two further, biosynthetically related, but nitrogen-free natural products, ancistronaphthoic acid B and cis-isoshinanolone, have been isolated from Ancistrocladus likoko J. LEACUTE;ONARD (Ancistrocladaceae). The 5,8'-coupling of the new alkaloids and of the alkaloids isolated earlier hints at a close phylogenetic relationship of A. likoko to other Central African Ancistrocladus species. The compounds show moderate activities against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei rhodesiense.     

Extract screening by HPLC coupled to MS-MS,NMR, and CD: a dimeric and three monomeric naphthylisoquinoline alkaloids from Ancistrocladus griffithii

Three new monomeric naphthylisoquinoline alkaloids, ancistrogriffines A, B, and C, and the first dimer of a 7,8'-coupled naphthylisoquinoline, ancistrogriffithine A, have been detected by phytochemical online screening of plant extracts of Ancistrocladus griffithii, using the analytical 'triad' HPLC-MS/MS, HPLC-NMR, and HPLC-CD. Ancistrogriffithine A, as well as ancistrogriffines A and C, were structurally completely assigned (including the absolute configuration) right from the extract, without previous isolation. Furthermore, two related, but known alkaloids, ancistrocladine and hamatine, were identified. Except for ancistrogriffine B, which occurs in trace quantities only, all new alkaloids were then isolated preparatively and the initial assignments were fully confirmed by conventional offline methods. Of particular interest is the constitutionally and configurationally unprecedented structure of ancistrogriffithine A, which is simultaneously the first dimeric naphthylisoquinoline alkaloid from an Asian Ancistrocladus species. Ancistrogriffithine A and ancistrogriffine A are active against Plasmodium falciparum. Furthermore, the latter compound shows good activity against Leishmania donovani. The results demonstrate the ability of modern online methods like HPLC-NMR, -MS/MS, and -CD to serve as powerful tools for the reliable structural elucidation of even complex structures of trace compounds in crude biological matrices.     

Phenolic analogs of the N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A, from Ancistrocladus cochinchinensis (Ancistrocladaceae), with improved antiprotozoal activities

The first N,8′-coupled naphthylisoquinoline alkaloids with free phenolic OH groups, 4′-O-demethylancistrocladinium A and 6,4′-O-didemethylancistrocladinium A, have been isolated from the leaves and bark of the Vietnamese liana Ancistrocladus cochinchinensis, along with its known, non-phenolic parent compound, ancistrocladinium A, and four C,C-coupled representatives. The structure elucidation was achieved by chemical, spectroscopic, and chiroptical methods. The mono-phenolic alkaloid showed excellent activities in particular against the pathogen causing Chagas’ disease, Trypanosoma cruzi.     

Steroidal glycosides from the marine sponge Pandaros acanthifolium

The chemical composition of the Caribbean sponge Pandaros acanthifolium was investigated and led to the isolation of seven new steroidal glycosides namely pandarosides A-D (1, 3, 4 and 6) along with the three methyl esters of pandarosides A, C, and D (2, 5 and 7). Their structures were characterized as 3β-[β-glucopyranosyl-(1→2)-β-glucopyranosyloxyuronic acid]-16-hydroxy-5α,14β-poriferast-16-ene-15,23-dione (1) and its methyl ester (2), 3β-[β-glucopyranosyloxyuronic acid]-16-hydroxy-5α,14β-poriferast-16-ene-15,23-dione (3), 3β-[β-glucopyranosyl-(1→2)-β-glucopyranosyloxyuronic acid]-16-hydroxy-5α,14β-cholest-16-ene-15,23-dione (4) and its methyl ester (5), 3β-(β-glucopyranosyloxyuronic acid)-16-hydroxy-5α,14β-cholest-16-ene-15,23-dione (6) and its methyl ester (7) on the basis of detailed spectroscopic analyses, including 2D NMR and HRESIMS studies. Pandarosides A-D and their methyl esters (1-7) are all characterized by a rare 2-hydroxycyclopentenone D-ring with a 14β configuration. The absolute configuration of the aglycon part of pandaroside A (1) was assigned by comparison between experimental and TDDFT calculated circular dichroism spectra on the more stable conformer.     

Trypanocidal tetrahydrofuran lignans from Peperomia blanda

Five tetrahydrofuran lignans and two known flavones were isolated from the aerial parts of Peperomia blanda. The structures of the isolated lignans were elucidated by interpretation of their spectroscopic data, including by gHMQC and gHMBC. The relative and absolute configurations of the isolates were determined from NOESY interactions and optical properties, respectively. Four of the lignans were diastereomeric whilst one was of mixed biosynthetic origin. All but one of the lignans exhibited high in vitro trypanocidal activity when assayed against epimastigotes of Trypanosoma cruzi strain Y.     

Ring A-seco triterpenoids with antibacterial activity from Dysoxylum hainanense

Five new ring A-seco triterpenoids, dysoxyhainic acids F-J (1-5), along with a known ring A-seco triterpenoid koetjapic acid (6) were isolated from the twigs and leaves of Dysoxylum hainanense. Their structures were established on the basis of extensive spectroscopic analysis. Antimicrobial activity of all the compounds against fungi and bacteria were tested. Compounds 2-4 and 6 exhibited significant antimicrobial activity against Gram-positive bacteria, and the antibacterial SAR (structure-activity relationship) was also briefly discussed.     

Structural elucidation and immuno-stimulating activity of an acidic heteropolysaccharide (TAPA1) from Tremella aurantialba

A novel acidic heteropolysaccharide (TAPA1) was purified from hot water extracts of Tremella aurantialba fruiting bodies by DEAE-Sepharose Fast Flow and Sephacryl S-500 High-Resolution Chromatography. The heteropolysaccharide had a molecular weight of ca. 1.35 × 10⁶ Da, and a carbohydrate content estimated to be ∼98.7% by the phenol-sulfuric acid method. It was composed mainly of d-mannose, d-xylose, and d-glucuronic acid in the ratio of ca. 5:4:1, along with trace amounts of d-galacturonic acid and d-glucose. Monosaccharide compositional analysis and GC-MS of methylated derivatives, combined with ¹H and ¹³C NMR spectroscopies (including COSY, TOCSY, NOESY, HSQC, and HMBC spectra), revealed TAPA1 to consist of an α-(1→3)-linked mannopyranosyl backbone, partially substituted at position 4 with xylose side chains, and at position 2 with side chains composed of either xylose, mannose, and glucuronic acid or of xylose and mannose. Bioactivity testing showed that TAPA1 stimulated the proliferation of mouse spleen lymphocytes in vitro.     

Structural features of immunologically active polysaccharides from Ganoderma lucidum.

Three polysaccharides, two heteroglycans (PL-1 and PL-4) and one glucan (PL-3), were solubilized from the fruit bodies of Ganoderma lucidum and isolated by anion-exchange and gel-filtration chromatography. Their structural features were elucidated by glycosyl residue and glycosyl linkage composition analyses, partial acid hydrolysis, acetolysis, periodate oxidation, 1D and 2D NMR spectroscopy, and ESI-MS experiments. The data obtained indicated that PL-1 had a backbone consisting of 1,4-linked alpha-D-glucopyranosyl residues and 1,6-linked beta-D-galactopyranosyl residues with branches at O-6 of glucose residues and O-2 of galactose residues, composed of terminal glucose, 1,6-linked glucosyl residues and terminal rhamnose. PL-3 was a highly branched glucan composed of 1,3-linked beta-D-glucopyranosyl residues substituted at O-6 with 1,6-linked glucosyl residues. PL-4 was comprised of 1,3-, 1,4-, 1,6-linked beta-D-glucopyranosyl residues and 1,6-linked beta-D-mannopyranosyl residues. These polysaccharides enhanced the proliferation of T- and B-lymphocytes in vitro to varying contents and PL-1 exhibited an immune-stimulating activity in mice.     

Chromenes of polyketide origin from Peperomia villipetiola

An extract of leaves and stems of Peperomia villipetiola has been found to contain myristicin (3-methoxy-4,5-methylenedioxy-allylbenzene) and seven chromenes, whose structures are methyl 5-hydroxy-7-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (1), methyl 5-methoxy-7-methyl-2,2-dimethyl-2H-1-chromene-8-carboxylate (2), methyl 7-hydroxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (3), methyl 7-methoxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (4), 5-methanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (5), 5-methanol-7-methoxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (6), and methyl 5-acetoxymethanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate (7). A biosynthetic rationale for 1-7 suggests that orsellinic acid may be a common intermediate. The anti-fungal activities of the chromenes were measured bioautographically against Cladosporium cladosporioides and Cladosporium sphaerospermum: compounds 6 and 7 were found to be the most active.     

An unusual quinolinone alkaloid from Waltheria douradinha

The chemical investigation of the methanolic extract of the root bark of Waltheria douradinha (Sterculiaceae) afforded an unusual quinolinone alkaloid named waltherione-A (1). Its structure was determined mainly by NMR spectroscopic methods. The antibacterial activity of waltherione-A (1) and the corresponding O-methylated derivative (2) was tested against three gram-negative and three gram-positive bacteria, with only (2) having moderate activity.     

Albizosides D and E, two new cytotoxic triterpene saponins from Albizia chinensis

Two oleanane-type triterpene saponins, named albizosides D and E (1 and 2), together with a known compound, Julibroside J₈ (3), were isolated from the stem bark of Albizia chinensis. The structures of compounds 1 and 2 were established by 1D, 2D NMR experiments, and chemical methods, and they showed moderate cytotoxic activity against a small panel of human tumor cell lines.     

Newbouldiaquinone A: A naphthoquinone-anthraquinone ether coupled pigment, as a potential antimicrobial and antimalarial agent from Newbouldia laevis

The study of the chemical constituents of the roots of Newbouldia laevis (Bignoniaceae) has resulted in the isolation and characterization of a naphthoquinone-anthraquinone coupled pigment named newbouldiaquinone A (1) together with 14 known compounds: apigenin, chrysoeriol, newbouldiaquinone, lapachol, 2-methylanthraquinone, 2-acetylfuro-1,4-naphthoquinone, 2,3-dimethoxy-1,4-benzoquinone, oleanolic acid, canthic acid, 2-(4-hydroxyphenyl)ethyl triacontanoate, newbouldiamide, 5,7-dihydroxydehydroiso-alpha-lapachone, beta-sitosterol, and beta-sitosterol glucopyranoside. The structure elucidation of the isolated compounds was established based on spectroscopic studies, notably of the 2D NMR spectra. The antimalarial activity of compound (1) against Plasmodium falciparum in vitro shows moderate chemo suppression of parasitic growth. Its antimicrobial activity against a wide range of microorganisms was 13- and 24-fold more active against Candida gabrata and Enterobacter aerogens than the reference antibiotics nystatin and gentamycin.     

Globulixanthones C,D and E: three prenylated xanthones with antimicrobial properties from the root bark of Symphonia globulifera

Two prenylated xanthone derivatives, named globulixanthones C and D and one bis-xanthone, designated globulixanthone E, have been isolated from the root bark of Symphonia globulifera. The structures of these compounds were elucidated by a detailed spectroscopic analysis. They have been shown to exhibit in vitro significant antimicrobial activity against a range of micro-organisms.     

The primary in vivo steroidal alkaloid glucosyltransferase from potato

To provide tools for breeders to control the steroidal glycoalkaloid (SGA) pathway in potato, we have investigated the steroidal alkaloid glycosyltransferase (Sgt) gene family. The committed step in the SGA pathway is the glycosylation of solanidine by either UDP-glucose or UDP-galactose leading to α-chaconine or α-solanine, respectively. The Sgt2 gene was identified by deduced protein sequence homology to the previously identified Sgt1 gene. SGT1 has glucosyltransferase activity in vitro, but in vivo serves as the UDP-galactose:solanidine galactosyltransferase. Two alleles of the Sgt2 gene were isolated and its function was established with antisense transgenic lines and in vitro assays of recombinant protein. In tubers of transgenic potato (Solanum tuberosum) cvs. Lenape and Desirée expressing an antisense Sgt2 gene construct, accumulation of α-solanine was increased and α-chaconine was reduced. Studies with recombinant SGT2 protein purified from yeast show that SGT2 glycosylation activity is highly specific for UDP-glucose as a sugar donor. This data establishes the function of the gene product (SGT2), as the primary UDP-glucose:solanidine glucosyltransferase in vivo.     

Rourinoside and rouremin, antimalarial constituents from Rourea minor

Bioassay-directed fractionation of the antimalarial active CHCl(3) extract of the dried stems of Rourea minor (Gaertn.) Aubl. (Connaraceae) liana led to isolation of two glycosides, rourinoside (1) and rouremin (2), as well as five known compounds, 1-(26-hydroxyhexacosanoyl)-glycerol (3), 1-O-beta-D-glucopyranosyl-(2S,3R,4E-8Z)-2-N-(2'-hydroxypalmitoyl)-octadecasphinga-4,8-dienine, 9S,12S,13S-trihydroxy-10E-octadecenoic acid, dihydrovomifoliol-9-beta-D-glucopyranoside, and beta-sitosterol glucoside. Compounds 1-3 showed weak in vitro activities against Plasmodium falciparum. Their structures and stereochemistry were elucidated by spectroscopic methods and selected enzyme hydrolysis.     

Thesinine-4'-O-beta-D-glucoside the first glycosylated plant pyrrolizidine alkaloid from Borago officinalis

The glycosylated pyrrolizidine alkaloid, thesinine-4'-O-beta-D-glucoside, has been isolated from the aqueous methanol extract of dried, defatted seeds of Borago officinalis (Boraginaceae). The structure was established by means of spectroscopic and chemical analysis.     

Antimalarial xanthones from Calophyllum caledonicum and Garcinia vieillardii

The antimalarial activity of 22 xanthones against chloroquino-resistant strains of Plasmodium falciparum was evaluated. Natural caloxanthone C (1), demethylcalabaxanthone (2), calothwaitesixanthone (3), calozeyloxanthone (4), dombakinaxanthone (5), macluraxanthone (6), and 6-deoxy-gamma-mangostin (7) were isolated from Calophyllum caledonicum. 1,6-dihydroxyxanthone (8), pancixanthone A (9), isocudraniaxanthone B (10), isocudraniaxanthone A (11), 2-deprenylrheediaxanthone B (12) and 1,4,5-trihydroxyxanthone (13) were isolated from Garcinia vieillardii. Moreover, synthetic compounds (14-22) are analogues or intermediates of xanthones purified from Calophyllum caledonicum (Oger J.M., Morel C., Helesbeux J.J., Litaudon M., Seraphin D., Dartiguelongue C., Larcher G., Richomme P., Duval O. 2003. First 2-Hydroxy-3-Methylbut-3-Enyl substituted xanthones isolated from Plants: structure elucidation, synthesis and antifungal activity. Natural Product Research 17(3), 195-199; Helesbeux J.J., Duval O., Dartiguelongue C., Seraphin D., Oger J.M., Richomme P., 2004. Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors. Tetrahedron 60(10), 2293-2300). The relationship between antimalarial activity and molecular structure of xanthones has also been explored. The most potent xanthones (2), (3) and (7) (IC50 = c.a. 1.0 microg/mL) are 1,3,7 trioxygenated and prenylated on the positions 2 and 8.