St John's wort and major depression.
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Major Depressive Disorder↗
Biomedical subjects
J H Cardellina
Publications and source records attributed to J H Cardellina.
Absolute stereochemistry and anti-HIV activity of minquartynoic acid, a polyacetylene from Ochanostachys amentacea.
Anti-HIV bioassay-guided fractionation of an organic extract of Ochanostachys amentacea provided an HIV-inhibitory polyacetylenic acid. The identity of this compound was established as (-)-17-hydroxy-9,11,13,15-octadecatetraynoic acid (1), also known as minquartynoic acid, by comparison of its physical and spectral data with previously reported values. Analysis of Mosher's ester derivatives of the methyl ester of 1 allowed assignment of S absolute stereochemistry to the lone chiral center. In an in vitro XTT-based anti-HIV assay, 2-5 micrograms/mL of minquartynoic acid (1) effectively inhibited human lymphoblastoid cell killing by HIV-1.
Alkynes↗
Cycloviolins A-D, anti-HIV macrocyclic peptides from Leonia cymosa.
Four novel anti-HIV macrocyclic peptides containing 28-31 amino acid residues, named cycloviolins A-D, have been isolated from the hitherto unstudied tropical plant Leonia cymosa. Their primary structure, including amino acid composition and sequence, was determined by a combination of MALDI-TOF and FAB MS and by enzymatic digestion of reduced derivatives, followed by Edman degradation and mass analyses. All of the cycloviolins contain six cysteines, which are present as three intramolecular disulfide bridges. Intriguingly, cycloviolins A-D showed high degrees of sequence homology to the known cyclopsychotride A and circulins A and B from the Rubiaceae family but much less homology to the varv peptides from Viola, a member of the same family (Violaceae).
Amino Acid Sequence↗
HIV-Inhibitory prenylated xanthones and flavones from Maclura tinctoria.
The organic extract of the plant Maclura tinctoria exhibited moderate anti-HIV activity. Seven prenylated phenolic derivatives were isolated from the active fractions and characterized by spectroanalytical methods. New compounds macluraxanthone B (1), macluraxanthone C (2), and dihydrocudraflavone B (8) were identified.
Anti-HIV Agents↗
New circulin macrocyclic polypeptides from Chassalia parvifolia.
Four new macrocyclic polypeptides were isolated and identified from an extract of the tropical tree Chassalia parvifolia. Circulins C-F are 29-30 amino acid cyclic peptides in which the entire primary amino acid chain is covalently cyclized via peptide bonds. Their structures were deduced from a combination of FABMS analyses, N-terminal Edman degradation, endoproteinase digestion, and amino acid analyses. All the peptides share a high degree of sequence homology and contain six cysteine residues forming three intramolecular disulfide bridges. Circulins C-F inhibited the cytopathic effects of in vitro HIV-1 infection with EC(50) values of 50-275 nM.
Alkylation↗
Cytotoxic and tubulin-interactive hemiasterlins from Auletta sp. and Siphonochalina spp. sponges.
Chemical and biological investigations of extracts from the sponge genus Auletta and two collections of Siphonochalina sp. have shown these organisms to be producers of the potent hemiasterlin class of antitumor agents. In addition to the previously known hemiasterlin (1) and hemiasterlin A (2), a new analogue, hemiasterlin C (3), was isolated and identified. The structures of 1 and 2 were assigned based on comparison to literature values, and 3 was identified on the basis of 1H NMR, 13C NMR, COSY, HSQC, and HMBC experiments. The cytotoxic and antitubulin activities of 1-3 were evaluated. In a comparative assay for inhibition of tubulin polymerization, the hemiasterlins were more potent than dolastatin 15 and equipotent with cryptophycin 1, but were somewhat less potent than dolastatin 10.
Animals↗
Guttiferone F, the first prenylated benzophenone from Allanblackia stuhlmannii.
The HIV-inhibitory activity in extracts of Allanblackia stuhlmannii was tracked, via bioassay-guided fractionation, to a new member of the camboginol/guttiferone class of prenylated benzophenones, guttiferone F (1). The structure was solved by extensive NMR analyses and by acid-catalyzed conversion to 30-epi-cambogin (4). This is the first report of this compound type in the genus Allanblackia.
Anti-HIV Agents↗
Vismiaphenones D-G, new prenylated benzophenones from Vismia cayennensis.
Following anti-HIV bioassay-guided fractionation, four new prenylated benzophenones, vismiaphenones D-G (7-10), were isolated from extracts of leaves of Vismia cayennensis. The structures were elucidated by spectral analyses. Only vismiaphenone D (7) exhibited HIV-inhibitory activity in the NCI primary screen.
Anti-HIV Agents↗
Alertenone, a dimer of suberosenone from Alertigorgia sp.
Bioassay-guided fractionation of organic extracts of the gorgonian Alertigorgia sp. has yielded the previously known suberosenone (1), a cytotoxic tricyclic sesquiterpene of the quadrone class, and alertenone (2), a dimer of suberosenone. The structure of 2 was determined by spectral analysis; the 1D TOCSY experiment was particularly useful in the structure elucidation. Comparison of the in vitro cytotoxicity of alertenone and suberosenone revealed that the dimeric alertenone was devoid of cytotoxicity below 35 microg/mL. In a hollow-fiber assay model of in vivo activity, suberosenone exhibited some growth inhibition of two of six tumor cell lines tested.
Animals↗
A new discorhabdin from two sponge genera.
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Animals↗
Isolation and characterization of adociavirin, a novel HIV-inhibitory protein from the sponge Adocia sp.
Aqueous extracts of the New Zealand sponge Adocia sp. (Haplosclerida) displayed potent anticytopathic activity in CEM-SS cells infected with HIV-1. Protein fractions of the extract bound both to the viral coat protein gp120 and to the cellular receptor CD4, but not to other tested proteins. The purified active protein, named adociavirin, was characterized by isoelectric focusing, amino acid analysis, MALDI-TOF mass spectrometry and N-terminal sequencing. Adociavirin, a disulfide-linked homodimer with a native molecular weight of 37 kDa, was active against diverse strains and isolates of HIV-1, as well as HIV-2, with EC50 values ranging from 0.4 nM to > 400 nM. The anti-HIV potency of adociavirin appears dependent on host cell type, with macrophage cultures being the most sensitive and peripheral blood lymphocytes the most resistant.
Amino Acid Sequence↗
Korundamine A, a novel HIV-inhibitory and antimalarial "hybrid" naphthylisoquinoline alkaloid heterodimer from Ancistrocladus korupensis.
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.
Animals↗
Structure-activity requirements for flavone cytotoxicity and binding to tubulin.
A series of 79 flavones related to centaureidin (3,6,4'-trimethoxy-5, 7,3'-trihydroxyflavone, 1) was screened for cytotoxicity in the NCI in vitro 60-cell line human tumor screen. The resulting cytotoxicity profiles of these flavones were compared for degree of similarity to the profile of 1. Selected compounds were further evaluated with in vitro assays of tubulin polymerization and [3H]colchicine binding to tubulin. Maximum potencies for tubulin interaction and production of differential cytotoxicity profiles characteristic of 1 were observed only with compounds containing hydroxyl substituents at C-3' and C-5 and methoxyl groups at C-3 and C-4'.
Antineoplastic Agents, Phytogenic↗
HIV-inhibitory and cytotoxic oligostilbenes from the leaves of Hopea malibato.
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.
Anti-HIV Agents↗
Isolation, primary sequence determination, and disulfide bond structure of cyanovirin-N, an anti-HIV (human immunodeficiency virus) protein from the cyanobacterium Nostoc ellipsosporum.
A novel anti-HIV protein, cyanovirin-N (CV-N), was isolated from an aqueous cellular extract of the cultured cyanobacterium (blue-green alga) Nostoc ellipsosporum, purified by reverse-phase HPLC, and sequenced by N-terminal Edman degradation of the intact protein and peptide fragments produced by endoproteinase digestions. CV-N consists of a single 101 amino acid chain which exhibits significant internal sequence duplication, but no significant homology to previously described proteins or to the transcription products of known nucleotide sequences. Alignment of residues 1-50 with residues 51-101 reveals 13 conservative amino acid changes as well as direct homology between 16 amino acid residues. CV-N contains four cysteines which form two intrachain disulfide bonds. The positions of the disulfide linkages were established by fast atom bombardment mass spectral studies of peptide fragments generated by a tryptic digestion of the native protein. Reductive cleavage of these crosslinks resulted in loss of anti-HIV activity.
Amino Acid Sequence↗
Isolation and characterization of niphatevirin, a human-immunodeficiency-virus-inhibitory glycoprotein from the marine sponge Niphates erecta.
Anti-human immunodeficiency virus (HIV)-bioassay-guided fractionation of aqueous extracts of the Caribbean sponge Niphates erecta led to isolation of a novel anti-HIV protein, named niphatevirin. The protein was purified to homogeneity by ethanol precipitation, ammonium sulfate precipitation, gel-permeation chromatography and concanavalin-A-Sepharose affinity chromatography. Niphatevirin potently inhibited the cytopathic effects of HIV-1 infection in cultured human lymphoblastoid (CEM-SS) cells; the effective concentration of drug that results in 50% protection of the cells through inhibition of cell lethality, cell-cell fusion and syncytium formation was approximately 10 nM. Delay of addition of niphatevirin to infected cultures by two hours markedly decreased (approximately 50%) cytoprotection; delay of addition by eight hours resulted in no antiviral activity. Niphatevirin bound to CD4 in a manner that prevented the binding of gp120, but did not directly bind gp120. Niphatevirin (6.5 microM) was inactive in both hemagglutination and hemolysis assays. Niphatevirin had a molecular mass of about 19 kDa by matrix-assisted laser-desorption ionization-time of flight (MALDI-TOF) mass spectrometry, and a native molecular mass of approximately 18 kDa by gel-filtration chromatography. The protein had an acidic isoelectric point of 4.2-4.6, and was shown by periodate acid Schiff's staining to be glycosylated.
Agglutination Tests↗
Isolation and characterization of novel cytotoxic saponins from Archidendron ellipticum.
A series of new ester saponins, elliptosides A-J, has been isolated from the tropical plant Archidendron ellipticum (Leguminosae). These saponins were particularly cytotoxic to certain renal and melanoma cancer cell lines in the NCI's 60-cell line human tumor screen. The structures of elliptosides A, E, and F were elucidated by spectroscopic and chemical means. Elliptoside A showed in vivo antitumor activity against the LOX melanoma cell line.
Antineoplastic Agents, Phytogenic↗
Novel cytotoxic, alkylated hydroquinones from Lannea welwitschii.
Two novel natural products, lanneaquinol (1) and 2'(R)-hydroxylanneaquinol (2), were isolated from the organic extract of the plant Lannea welwitschii (Hiern) Engl. Their structures were solved by spectroanalytical methods and confirmed by comparison to synthetic models. The absolute configuration of 2 was determined by the modified Mosher method. Both compounds exhibited modest cytotoxicity against the NCI panel of 60 human tumor cell lines. The structures of two isomeric 4,5-dihydroxy-5-alkyl-2-cyclohexenones (7 and 8), which appear to be biogenetic precursors of 1 and 2, were also elucidated.
Alkylation↗