RESUMO
Four macrocyclic trichothecenes, roridin A, roridin E, verrucarin A and verrucarin J, produced by the hypocrealean epibiont of Baccharis coridifolia, were evaluated for their inhibitory activity against the arenavirus Junin (JUNV), the etiological agent of Argentine hemorrhagic fever. The trichothecenes achieved a dose-dependent inhibition of JUNV multiplication at concentrations not affecting cell viability. The 50 % inhibitory concentration (IC50) values determined by a virus yield inhibition assay were in the range 1.2 - 4.9 ng/ml. The most active compound was verrucarin J which reduced JUNV yield more than 2 log units and had a similar effect against the arenavirus Tacaribe. The trichothecenes lacked virucidal effects on JUNV virions. From time of addition and removal experiments, it can be concluded that verrucarin J inhibited a late stage in the replicative cycle of JUNV, after 5 h of adsorption.
Assuntos
Antivirais/farmacologia , Asteraceae/virologia , Vírus Junin/efeitos dos fármacos , Tricotecenos/farmacologia , Animais , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Vírus Junin/crescimento & desenvolvimento , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Tricotecenos/química , Células VeroRESUMO
Two new trisulfated triterpene glycosides, liouvillosides A (1) and B (2), have been isolated from the Antarctic sea cucumber Staurocucumis liouvillei. Their structures have been elucidated by spectroscopic analysis (NMR and FABMS) and chemical transformations. Liouvillosides A (1) and B (2) are two new examples of a small number of trisulfated triterpene glycosides from sea cucumbers belonging to the family Cucumariidae. Both glycosides were found to be virucidal against herpes simplex virus type 1 (HSV-1) at concentrations below 10 microg/mL.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Oligossacarídeos/isolamento & purificação , Pepinos-do-Mar/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Antivirais/isolamento & purificação , Configuração de Carboidratos , Chlorocebus aethiops , Ensaios de Seleção de Medicamentos Antitumorais , Herpesvirus Humano 1/efeitos dos fármacos , Hidrólise , Espectroscopia de Ressonância Magnética , Metilação , Testes de Sensibilidade Microbiana , Oligossacarídeos/química , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Células VeroRESUMO
Disodium 3beta,21-dihydroxypregn-5-en-20-one disulfate (2), sodium 3beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3), sodium 3beta,21-dihydroxypregn-5-en-20-one 21-sulfate (4), and disodium 3beta,6alpha-dihydroxy-5alpha-pregnan-20-one disulfate (6) have been synthesized and completely characterized for the first time from readily available materials. Sulfation was performed using triethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. Selective sulfation of 3beta,21-dihydroxypregn-5-en-20-one rendered sodium 3beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3) as the major compound. The synthetic sulfated steroids as well as natural disulfated polyhydroxysteroids (7-9) isolated by us from the antarctic ophiuroid Astrotoma agassizii and the synthetic derivatives disodium 2beta,3alpha,21-trihydroxy-(20R)-cholesta-5,24-diene 3-acetate, 2,21-disulfate (7a) and 2beta,3alpha,21-trihydroxy-(20R)-cholesta-5,24-diene (7b) were comparatively evaluated for their inhibitory effect on the replication of one DNA (HSV-2) and two RNA (PV-3, JV) viruses. In general, steroids with sulfate groups at C-21 and C-2 or C-3 were the most effective in their inhibitory action against HSV-2 and also proved to be active against PV-3 and JV.
Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Colesterol/análogos & derivados , Sulfatos/química , Animais , Morte Celular/efeitos dos fármacos , Chlorocebus aethiops , Colesterol/síntese química , Colesterol/farmacologia , Replicação do DNA/efeitos dos fármacos , Equinodermos/química , Herpesvirus Humano 2/efeitos dos fármacos , Vírus Junin/efeitos dos fármacos , Poliovirus/efeitos dos fármacos , Células Vero/efeitos dos fármacosRESUMO
From the water-insoluble lipid fraction of the methylene chloride/methanol extract of the starfish Cosmasterias lurida, two new glucosylceramides together with a known glucosylceramide, ophidiacerebroside E, were isolated by chromatographic procedures and characterized by spectroscopic (1H and 13C nuclear magnetic resonance, mass spectrometry) methods. The new compounds were identified as (2S,3R,4E,8E,10E)-1-(beta-D-glucopyranosyloxy)-3 -hydroxy-2-[(R)-2-hydroxyheptadecanoyl)amino]-9-methyl-4,8,10-o ctadecatriene (3) and (2S,3R,4E,8E,10E)-1-(beta-D-glucopyranosyloxy)-3 -hydroxy-2-[(R)-2-hydroxyoctadecanoyl)amino]-9-methyl-4,8,10-oc tadecatriene (4).
Assuntos
Glucosilceramidas/química , Glucosilceramidas/isolamento & purificação , Estrelas-do-Mar/química , Animais , Sequência de Carboidratos , Cromatografia Líquida de Alta Pressão , Dados de Sequência Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
One new and three known sulfated steroidal polyols have been isolated from the ophiuroid Ophioplocus januarii, collected at San Antonio Oeste, Río Negro, Argentina. The four compounds possess 4 alpha,11 beta-dihydroxy-3 alpha,21-disulfoxy substituents and the A/B cis ring junction but differ in the side chain. The new compound has been characterized as (22E)-5 beta-24-norcholest-22-ene-3 alpha,4 alpha,11 beta,21-tetrol 3,21-disulfate (4). The structures of the four compounds were determined from spectral data and comparison with those of related steroidal polyols. The four compounds were tested for their inhibitory effect on the replication of one DNA and three RNA viruses. Compounds 2 and 4 were active against respiratory syncytial and polio viruses, and compound 3 inhibited Junin virus, responsible for Argentine hemorrhagic fever.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Estrelas-do-Mar/química , Esteróis/isolamento & purificação , Replicação Viral/efeitos dos fármacos , Animais , Fármacos Anti-HIV/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Efeito Citopatogênico Viral/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Vírus de DNA/efeitos dos fármacos , Vírus de DNA/metabolismo , Vírus de RNA/efeitos dos fármacos , Vírus de RNA/metabolismo , Esteróis/farmacologiaRESUMO
Four new sulfated asterosaponins, designated as cosmasterosides A [1], B [2], C [4], and D [5], have been isolated from the Atlantic starfish Cosmasterias lurida along with large amounts of the pentaglycoside ophidianoside F [3] and the minor component forbeside H [6], previously isolated from Ophidiaster ophidianus and Asterias forbesi, respectively. Cosmasteroside A [1] contains the same oligosaccharide chain as ophidianoside F [3] and a (20S)-5 alpha-cholesta-9(11),24-diene-3 beta,6 alpha,20-triol-3 beta-sulfated aglycone. Cosmasterosides B [2], C [4], and D [5] are based on the known aglycone, thornasterol A, and differ in the number and type of monosaccharide components of the carbohydrate chain. Cosmasteroside B [2] contains a novel oligosaccharide chain that differs from that of ophidianoside F [3] by the replacement of the quinovose unit attached to C-6 of the steroidal aglycone by glucose. The tetraglycosides cosmasterosides C [4] and D [5] are structurally related to ophidianoside F [3] and cosmasteroside B [2], respectively, by the loss of a terminal fucose unit.
Assuntos
Glicosídeos/química , Oligossacarídeos/química , Saponinas/química , Estrelas-do-Mar/química , Animais , Sequência de Carboidratos , Feminino , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Ovário/químicaRESUMO
Two novel steroidal monoglycoside sulfates, luridosides A [1] and B [2], have been isolated from the starfish Cosmasterias lurida. These compounds co-occur with one known steroidal monoglycoside, pycnopodioside C [3]. The structures of the new metabolites were determined from spectral data and comparison with those of related steroids.