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Phytoactive substances were present in a culture broth of Drechslera gigantea, a pathogenic fungus of several grasses. Twelve eremophilane sesquiterpenes (1, 2, 3, 4, 6, 7, 10, 11, 12, 13, 14, and 15) were isolated and structurally characterized by a combination of single-crystal X-ray diffraction and spectroscopic analyses. Most of these sesquiterpenoids were phytotoxic; however, compounds 1 and 3 caused chlorophyll retention, an activity previously associated with phytohormones.

A unique heterodimeric naphthylisoquinoline alkaloid, korundamine A (2), comprised of two different monomeric biaryl halves, has been isolated from the Cameroonian tropical liana Ancistrocladus korupensis. Korundamine A is the first “hybrid” dimer found in the Ancistrocladaceae; in vitro , it demonstrated anticytopathic activity against HIV-1 and antimalarial activity against Plasmodium falciparum.

(-)-Frondosins A and D, two sesquiterpene hydroquinone metabolites, were isolated and identified from the HIV-inhibitory organic extracts of the marine sponge Euryspongia sp. In contrast to the dec...

New monomeric (korupensamine E, 6) and dimeric (michellamines D-F, 7-9) naphthylisoquinoline alkaloids have been isolated from extracts of the tropical liana Ancistrocladus korupensis. Structures were determined by spectroanalytical methods, and stereochemistry was defined through NOE correlations, chemical degradation, and CD spectroscopy. Michellamines D-F exhibited in vitro HIV-inhibitory activity comparable to michellamine B, and korupensamine E exhibited in vitro antimalarial activity comparable to korupensamines A-D.

New monomeric naphthylisoquinoline alkaloids, yaoundamines A and B, were isolated from Ancistrocladus korupensis and their structures were determined by extensive chemical and spectroscopic analyses. The absolute configuration at C3 was established by chemical degradation, while the axial chirality was deduced by comparison of experimental and calculated CD spectra. Yaoundamine B has an unprecedented glycosylated naphthylisoquinoline structure. Yaoundamines A and B are active in vitro against the malaria parasite Plasmodium falciparum.

Using bioassay-guided fractionation, dioncophylline A [1] was isolated from the leaves and twigs of the tropical liana Ancistrocladus letestui Pelligr. Dioncophylline A was previously known from Triphyophyllum peltatum and A. abbreviatus. The in vitro cytotoxicity profile of 1 was characterized against the NCI panel of human tumor cell lines.

Here we report details of the isolation and determination of the abso- lute configurations and comparative anti-HIV activities of novel, atro- pisomeric naphthylisoquinoline alkaloid dimers, michellamines A, B, and C, from a newly described species of Ancistrocladus from the Korup rai- nforest of Cameroon. We further provide a more extensive analysis of the range of anti-HIV activity of michellamine B, the most potent and abundant member of the series. Michellamine B inhibited HIV-induced cell killing and viral replication in a variety of human cell lines, as well as in cultures of human peripheral blood leukocytes and monocytes. Michellamine B was active against a panel of biologically diverse labo- ratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6 and the pyridinone-resistant strain A17; the compound also in- hibited several strains of HIV-2

The circular dichroic behavior of the michellamines, dimeric naphthylisoquinoline alkaloids, was investigated. Due to the molecular size and conformational flexibility, which makes direct calculations of the CD spectra very difficult, and because of the lack of direct standards for an empirical comparison, there is no simple possibility for the interpretation of the CD spectra of such quateraryls. The chiroptical contributions of the particular stereogenic elements were shown to behave largely additively and thus allow comparison of spectra of the quateraryls with those of the corresponding ‘monomeric’ naphthylisoquinolines. This comparison was performed first of all with the experimental and theoretical CD spectra of ancistrobrevine B, then with the predicted spectra of the authentic molecular ‘halves’ of the michellamines.

A first synthetic access to michellamine A (1), a C2-symmetric antiviral naturally occurring quateraryl, is described, by oxidative ‘dimeriza

Triticones A [1], B [2], C [3], D [4], E [5], and F [6] were isolated from the culture broth of the plant pathogenic fungus Drechslera tritici-repentis(=Pyrenophoria tritici-repentis). The structures of these γ-lactams were determined by a combination of single crystal X-ray diffraction and spectroscopic analyses. A series of 2D nmr experiments has clarified the spectral assignments of triticones A [1] and B [2] and their interconversion

A detailed analysis of four different collections of the sponge genus Zyzzya yielded nine pyrroloiminoquinones of the makaluvamine, batzelline, and isobatzelline/damirone classes. Dereplication analyses of additional Zyzzya extracts did not disclose more potent or additional new compounds. Comparative testing of these compounds in the National Cancer Institute's 60 cell line human tumor screen revealed varying levels of potency and differential cytotoxicity, apparently related to the unsaturation levels in and substitution patterns on the core ring system. Further studies on the topoisomerase II-mediated DNA cleavage were conducted. Reductive activation of the pyrroloiminoquinones led to DNA damage in vitro, which correlated with half wave potentials and reversibility parameters. DNA damage could be abrogated by ascorbate. Fluorescence displacement was used to measure intercalation with DNA; intercalation efficiency did not correlate with DNA-damaging proficiency. Makaluvamine H (5) emerged as the most potent and differential of our isolates, roughly comparable to makaluvamines C (in vitro) and I (in vivo). 3,7-Dimethyl guanine was isolated from one of the Zyzzya collections and from the sponge Latrunculia purpurea. (c) 2005 Elsevier Ltd. All rights reserved.

Bioassay-guided fractionation of the organic extracts of whole plants of Mostuea brunonis (Loganiaceae), using the National Cancer Institute's (NCI) human tumor-based in vitro antitumor screen, led to the isolation and identification of camptothecin 20-O-beta-D-glucoside (1) and three moderately cytotoxic alkaloids, the known deoxypumiloside (2) and strictosamide (3), and the new 2'-O-acetylstrictosamide (4), from the cytotoxic alkaloid fractions. While the previously unknown 20-O-beta-D-glucopyranosyl camptothecin exhibited greater solubility in alcohol, DMSO-H(2)O and H(2)O than camptothecin, it was essentially inactive in the NCI's in vitro 60-cell line primary antitumor screen. However, it could be vulnerable to de-glucosidation in vivo, and may, therefore, merit additional evaluation as a potential prodrug of camptothecin that could be more readily formulated than the parent agent.

Three new oligostilbenes, malibatols A (1) and B (2) and dibalanocarpol (3), together with one known oligostilbene balanocarpol (4), were isolated from the organic extract of the leaves of Hopea malibato. The structure elucidation of these compounds was based on the interpretation of their chemical and spectral data. Compounds 3 and 4 exhibited very modest HIV-inhibitory activity, while compounds 1 and 2 were cytotoxic to the host cells (CEM SS) in the antiviral assay.

Antitumor bioassay-guided fractionation of the organic extract of the marine sponge Cribrochalina vasculum resulted in the isolation of several closely related cytotoxic acetylenic alcohols [1-8], the structures of which were assigned on the basis of chemical and spectral studies. 3-Hydroxyeicos-(4E)-en-1-yne [1], 3-hydroxydocosa-(4E,15Z)-dien-1-yne [2], 3-hydroxy-16-methyleicos-(4E)-en-1-yne [3], 3-hydroxy-19-methyleicos-(4E)-en-1-yne [4],3-hydroxy-21-methyldocosa-(4E,15Z)-dien-1-yne [5], and 3-hydroxy-14-methyldocosa-(4E)-en-1-yne [6] are enantiomers of known compounds, while 3-hydroxyheneeicos-(4E)-en-1-yne [7] and 5-hydroxy-16-methyleicos-(3Z)-en-1-yne [8] are new metabolites isolated as minor components. The absolute configuration of C-3 in 1-7 and C-5 in 8 has been assigned as S using the modified Mosher's method. Compounds selected from this series showed selective in vitro antitumor activity against the H-522 non-small cell lung line and the IGROV-1 ovarian line. Synthetic racemic 1 demonstrated a modest dose-related therapeutic activity in a preliminary in vivo xenograft assay based on the latter cell line.

Crude extracts of Ancistrocladus korupensis contain a complex mixture of naphthyltetrahydroisoquinoline alkaloids, including the human immunodeficiency virus-inhibitory dimeric alkaloids michellamines A and B and the antimalarial monomeric korupensamines A-D. The efficient separation of michellamines A and B from these extracts has been accomplished by centrifugal partition chromatography. The chromatographic conditions used on a multi-channel cartridge unit (Sanki LLN) have been successfully scaled up with a newly developed, stacked-disk type centrifugal partition chromatography unit (Sanki NMF) for separating larger amounts of alkaloid mixtures with similar resolution. A refined, three-step process (solvent-solvent partitioning, centrifugal partition chromatography and HPLC) has been developed and applied to the scaled-up production of michellamine B for preclinical drug development.

A new C43 acetylenic alcohol, vasculyne (1), was isolated by cytotoxicity-guided fractionation of the Caribbean sponge Cribrochalina vasculum. The structure of 1 was determined by spectroscopic methods.

The exciton chirality method, as applied to secondary allylic alcohols, cannot be extended to secondary alcohols flanked by two chromophores.

Curvulin was isolated from Drechslera indica and identified by X-ray crystallography. O -Methylcurvulinic acid was also isolated from this source and identified by NMR and HREIMS. Both compounds are phytotoxic to 2 of the normal hosts of this fungus when applied to detached leaves. Some plants are unaffected by these compounds. Host leaf constituents have some role in regulating the production of these phytotoxins by the fungus.

A phytotoxic metabolite has been isolated from cultures of Drechslera siccans and structurally characterized as 6,8-dihydroxy-3-(2′-hydroxypropyl) isocoumarin (de- O -methyldiaporthin).

The isolation, structure determination, and phytotoxicity of stemphyperylenol, stemphyltoxin II, alterperylenol, and altertoxin I from Alternaria cassiae are reported.

Gigantenone, a new eremophilane diepoxide, was isolated from the fungal plant pathogenDrechslera gigantea. It displays unique biological activity on higher plants. On most graminaceous species, the application of 18 nanomoles to a leaf surface results in the formation of ‘green islands’ — localized areas of chlorophyll retention. Gigantenone is structurally unrelated to the cytokinins, yet induces the green island effect associated with these phytohormones at comparable concentrations. However, on dicotyledonous species it generally causes necrotic lesions. On host plants ofD. gigantea, gigantenone induced lesions closely resembling those appearing in natural infections. Gigantenone also induces root formation in mung bean hypocotyls and shows a high level of activity in several plant tissue culture systems.