RESUMO
DNA polymerase beta (Pol beta) is an error-prone enzyme whose up-regulation has been shown to be a genetic instability enhancer as well as a contributor to cisplatin resistance in tumor cells. In this work, we describe the isolation of new Pol beta inhibitors after high throughput screening of 8448 semipurified natural extracts. In vitro, the selected molecules affect specifically Pol beta-mediated DNA synthesis compared with replicative extracts from cell nuclei. One of them, masticadienonic acid (MA), is particularly attractive because it perturbs neither the activity of the purified replicative Pol delta nor that of nuclear HeLa cell extracts. With an IC50 value of 8 microM, MA is the most potent of the Pol beta inhibitors found so far. Docking simulation revealed that this molecule could substitute for single-strand DNA in the binding site of Pol beta by binding Lys35, Lys68, and Lys60, which are the main residues involved in the interaction Pol beta/single-strand DNA. Selected inhibitors also affect the Pol beta-mediated translesion synthesis (TLS) across cisplatin adducts; MA was still the most efficient. Therefore, masticadienonic acid sensitized the cisplatin-resistant 2008C13*5.25 human tumor cells. Our data suggest that molecules such as masticadienonic acid could be suitable in conjunction with cisplatin to enhance anticancer treatments.
Assuntos
Cisplatino/farmacologia , DNA Polimerase beta/antagonistas & inibidores , DNA Polimerase beta/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/isolamento & purificação , Células HeLa , Humanos , Juniperus , Pistacia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta , Caules de Planta , RatosRESUMO
Two new withanolide glycosides, (20R,22R)-O-(3)-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl-1 alpha,12 beta-diacetoxy-20-hydroxywitha-5,24-dienolide (3) and (20R,22R)-O-(3)-beta-D-xylopyranosyl(1-->3)-[beta-D-xylopyranosyl(1-->4)]-beta-D-glucopyranosyl-1 alpha-acetoxy-12 beta,20-dihydroxywitha-5,24-dienolide (4), were isolated from the leaves and root of Dunalia brachyacantha. Their aglycones, (20R,22R)-1 alpha,12 beta-diacetoxy-3 beta,20-dihydroxywitha-5,24-dienolide (or 1 alpha,12 beta-diacetyldunawithagenine) and (20R,22R)-1 alpha-acetoxy-3 beta,12 beta,20-trihydroxywitha-5,24-dienolide (or 1 alpha-acetyl-12 beta-hydroxydunawithagenine), are novel. The known 18-acetoxywithanolide D (1) and 18-acetoxy-5,6-deoxy-5-withenolide D (2) were also isolated from the leaves. These last two compounds were shown to be responsible for the trypanocidal, leishmanicidal, and bactericidal activities manifested by the crude ethanolic extract. The structures were deduced from spectroscopic data and on the basis of chemical evidence.
Assuntos
Dissacarídeos/isolamento & purificação , Ergosterol/análogos & derivados , Lactonas/isolamento & purificação , Plantas Medicinais/química , Solanaceae/química , Trissacarídeos/isolamento & purificação , Tripanossomicidas/isolamento & purificação , Tripanossomicidas/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bolívia , Dissacarídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lactonas/química , Leishmania/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Raízes de Plantas/química , Espectrofotometria Infravermelho , Trissacarídeos/química , Trypanosoma cruzi/efeitos dos fármacos , VitanolídeosRESUMO
The isolation and spectral data of julocrotin (1), a glutarimide alkaloid from Croton membranaceus are reported.
Assuntos
Alcaloides/química , Euphorbiaceae , Plantas Medicinais , Humanos , Piperidonas/química , Extratos Vegetais/química , Raízes de PlantasRESUMO
The ethanolic extract from the stem bark of Dimocarpus fumatus, showed in vitro cytotoxic activity against KB cells. Fractionation of the extract gave compounds belonging to different classes. The two major components have been identified as a benzoquinone, sargaquinone, and a chromene, sargaol. One sphingolipid, soyacerebroside I, two glycosides of sitosterol, and fatty acids were also identified. Besides these known compounds, two new glycosides of long-chain fatty alcohols have been identified as 1-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D- glucopyranosyl]hexadecanol and 1-O-[[alpha-L-arabinopyranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1 -->2)- beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D- glucopyranosyl] hexadecanol, and a mixture of three new diacylglycerylglucosides has been isolated. These structures were elucidated by analysis of 2D-NMR and mass spectra.
Assuntos
Antineoplásicos Fitogênicos/química , Glicosídeos/química , Oligossacarídeos/química , Árvores , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Configuração de Carboidratos , Sequência de Carboidratos , Sobrevivência Celular/efeitos dos fármacos , Glicosídeos/isolamento & purificação , Glicosídeos/toxicidade , Humanos , Células KB , Leucemia P388 , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Oligossacarídeos/isolamento & purificação , Oligossacarídeos/toxicidade , Caules de Planta , Células Tumorais CultivadasRESUMO
A new aminosteroid, 3beta-amino-22,26-epiminocholest-5-ene named sarachine (1), and two known flavonoids, eriodictyol (2) and 7-O-beta-D-glucopyranosyl-eriodictyol (3), were isolated from the leaves of Saracha punctata. The alkaloid was found to inhibit the growth of Leishmania braziliensis promastigotes (100% at 25 microM) and of Trypanosoma cruzi epimastigotes in culture (50% at 25 microM) and showed a strong in vitro antiplasmodial activity with an IC50 of 25 nM.
Assuntos
Antiprotozoários/farmacologia , Colestenos/farmacologia , Plantas Medicinais/química , Animais , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antiprotozoários/isolamento & purificação , Colestenos/isolamento & purificação , Leishmania braziliensis/efeitos dos fármacos , Plasmodium berghei/efeitos dos fármacos , Tripanossomicidas/isolamento & purificação , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Four new saponins have been isolated from the stem bark of Filicium decipiens and identified as 3-O-{beta-D-glucopyranosyl(1-->2)-beta- D-glucopyranosyl}-28-O-{[alpha-L-arabinopyranosyl(1-->2)-beta- D-xylopyranosyl (1-->6)]. [4-O-angeloyloxy-alpha-L-arabinopyranosyl(1-->2)-alpha-L- rhamnopyranosyl(1-->2)]}-beta-D-glucopyranosyl gypsogenic acid, 3-O-{beta-D-glucopyranosyl(1-->2)-beta-D- glucopyranosyl}-28-O-{[alpha-L-arabinopyranosyl(1-->2)- beta-D-xylopyranosyl(1-->6)] [4-O-angeloyloxy-alpha-L- arabinopyranosyl(1-->2)-alpha-L-rhamnopyranosyl(1-->2)]}-beta-D- glucopyranosyl medicagenic acid, 3-O-{beta-D-glucopyranosyl(1-->2)-beta-D- glucopyranosyl}-28-O-{[alpha-L-arabinopyranosyl(1-->2)] [beta-D-xylopyranosyl(1-->4)]alpha-L-rhamnopyranosyl(1-->2)-4-O-[3'- hydroxy-2'-methyl-butyroyloxy)-3-hydroxy-2-methyl-butyroyloxy++ +]-beta-D- fucopyranosyl} medicagenic acid and 3-O-beta-D-glucopyranosyl-28-O- {[alpha-L-arabinopyranosyl(1-->2)] [beta-D-xylopyranosyl(1-->4)] alpha-L-rhamnopyranosyl(1-->2)-4- O-[(3'-hydroxy-2'-methyl-butyroyloxy)-3-hydroxy-2-methyl-butyro yloxy]-beta- D-fucopyranosyl} zanhic acid. These structures were elucidated by analysis of 2D-NMR spectra and of electrospray ionization mass spectra.
Assuntos
Saponinas/química , Árvores , Sequência de Carboidratos , Conformação Molecular , Dados de Sequência Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Caules de Planta/química , Saponinas/isolamento & purificação , Espectrometria de Massa de Íon Secundário , Relação Estrutura-AtividadeRESUMO
Five new saponins have been isolated from the stem bark of Harpullia cupanioides and identified as 3-O-beta-D-glucopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 22-O-angeloyl-A1-barrigenol, 3-O-beta-D-glucopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 28-O-angeloyl-A1-barrigenol, 3-O-beta-D-galactopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 28-O-angeloyl-A1-barrigenol. 3-O-beta-D-galactopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 16-O-beta, beta-dimethylacryloyl-camelliagenin A and 3-O-beta-D-glucopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 28-O-angeloyl-camelliagenin A. The structures were elucidated by analysis of 2D-NMR spectra and mass spectra.
Assuntos
Saponinas/química , Saponinas/isolamento & purificação , Árvores/química , Sequência de Carboidratos , Dados de Sequência Molecular , Ressonância Magnética Nuclear Biomolecular , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
1H NMR spectroscopy assignments have been obtained for starch acetates using COSY and HOHAHA experiments by comparison with the spectra of amylose triacetate and of peracetylated malto-oligosaccharides (maltotriose, maltotetraose, maltoheptaose). These assignments are valuable for the location and evaluation of the substitution pattern in modified starches. The bulk of the 1H NMR spectra of highly acetylated starch strongly resembles the spectrum of amylose triacetate in which all protons are identified and display distinct chemical shifts. The resolving power of the HOHAHA experiment allowed the distinction of minor spin systems. Beside these strong signals pertaining to an average 2.3.6-tri-O-acetyl-alpha-(1-->4) linked D-glucopyranose unit in an infinite chain, the combination of COSY and HOHAHA experiments allowed the identification of these systems to the terminal, n-1, n-2, and to partially acetylated glucopyranosyl units. As an example, two different preparations of starch acetates with degrees of substitution 2.74 and 2.63 were examined. In one case, NMR demonstrates that the defects of acetylation are random on the polymeric chain (with corresponding signals for unacylated secondary hydroxyl positions at delta 3.61 and 3.40) while in another case, these signals are not detectable, probably due to the presence of clusters of non-acetylated residue forming solid-like zones.
Assuntos
Glucose/química , Espectroscopia de Ressonância Magnética/métodos , Amido/análogos & derivados , Acetilação , Sequência de Carboidratos , Dados de Sequência Molecular , Oligossacarídeos/química , Prótons , Amido/químicaRESUMO
Six saponins were isolated from the leaves of Pisonia umbellifera. Three are new oleanolic acid saponins, and two of them contain an unusual seco-glycopyranosyl moiety. Their structures were determined using a combination of 1H and 13C NMR, and mass spectrometry as 3-O-{beta-D-glucopyranosyl(1-->2)[beta-D-glucopyranosyl (1-->2)-beta-D-xylopyranosyl(1-->3)]-beta-D-glucuronopyranosyl} 28-O-beta-D-glucopyranosyl olean-12-en-3 beta-ol-28-oic acid, 3-O-{2'-(2"-O-glycolyl)-glyoxylyl-beta-D-glucuronopyranos yl} 28-O-beta-D-glucopyranosyl olean-12-en-3 beta-ol-28-oic acid and 3-O-{2'-O-glycolyl)-glyoxylyl-beta-D-glucuronopyranosyl++ +} olean-12-en-3 beta-ol-28-oic acid.
Assuntos
Saponinas/isolamento & purificação , Árvores/química , Configuração de Carboidratos , Espectroscopia de Ressonância Magnética , Saponinas/química , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
Six saponins were isolated from the seed kernel of Mimusops elengi, M. hexandra and M. manilkara. Their structures were determined using a combination of 1H NMR, 13C NMR and mass spectroscopy. Three of them are new compounds: 3-O-(beta-D-glucuronopyranosyl) 28-O-(alpha-L-rhamnopyranosyl (1-->3) beta-D-xylopyranosyl(1-->4) [alpha-L-rhamnopyranosyl(1-->3)] alpha-L-rhamnopyranosyl(1-->2) alpha-L-arabinopyranosyl) protobassic acid, 3-O-(beta-D-glucuronopyranosly) 28-O-(alpha-L-rhamnopyranosyl(1-->3) beta-D-xylopyranosyl(1-->4) alpha-L-rhamnopyranosyl(1-->2) alpha-L-arabinopyranosyl) 16-alpha-hydroxyprotobassic acid and 3-O-(beta-D-glucopyranosyl(1-->3) beta-D-glucopyranosyl) 28-O-(alpha-L-rhamnopyranosyl(1-->3) beta-D-xylopyranosyl(1-->4) alpha-L-rhamnopyranosyl(1-->2) alpha-L-arabinopyranosyl) protobassic acid.
Assuntos
Plantas Medicinais/química , Saponinas/isolamento & purificação , Sequência de Carboidratos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Saponinas/química , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
The stem-bark of Dictyoloma peruviana yielded two new piperidino [1,2-a] 4-quinolinones, dictyolomide A and dictyolomide B. Their structures were established by NMR spectroscopy.
Assuntos
Alcaloides/química , Antiprotozoários/química , Piperidinas/química , Plantas Medicinais , Quinolonas/química , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Animais , Antiprotozoários/isolamento & purificação , Antiprotozoários/toxicidade , Leishmania/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Medicina Tradicional , Estrutura Molecular , Rotação Ocular , Piperidinas/isolamento & purificação , Piperidinas/toxicidade , Caules de Planta , Quinolonas/isolamento & purificação , Quinolonas/toxicidadeRESUMO
A novel derivative of sucrose, beta-(3,6-di-O-feruloyl)-fructofuranosyl-alpha-(2,3,4,6-tetra-O-ac etyl)- glucopyranoside, was isolated from the wood of Bhesa paniculata. Its structure was determined by a combination of 2D 1H-1H and 1H-13C correlation NMR spectroscopy. The known compounds, glycerol 1-9',12'-octadecadienoate, beta-sitosterol, (+/-)-pinoresinol, methyl 3,4-dihydroxybenzoate, 4-hydroxy-3-methoxybenzoic acid, anofinic acid and 2-(1'-methylethenyl)-benzofuran-5-carboxylic acid were also isolated.
Assuntos
Ácidos Cumáricos/química , Plantas Medicinais/química , Sacarose/análogos & derivados , Árvores/química , Configuração de Carboidratos , Sequência de Carboidratos , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Cumáricos/análise , Ácidos Cumáricos/isolamento & purificação , Indonésia , Espectroscopia de Ressonância Magnética , Malásia , Modelos Estruturais , Dados de Sequência Molecular , Sacarose/química , Sacarose/isolamento & purificaçãoRESUMO
Two new oleanolic acid saponins were isolated from the leaves and roots of Beta vulgaris. Both contained the unusual feature of a 3,4 seco-glycopyranosyl moiety. Their structures were established by a combination of 2D NMR experiments and of Californium plasma desorption mass spectrometry.
Assuntos
Glicosídeos/isolamento & purificação , Ácido Oleanólico/química , Verduras/química , Sequência de Carboidratos , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Dados de Sequência MolecularRESUMO
Quercitol, five saponins and 3-O-(6'-O-palmitoyl) beta-D-glucopyranosyl stigmasterol were isolated from the stem bark of Myrisine pellucida. These compounds are described for the first time in this plant and their structures were determined using a combination of 1H and 13C NMR, and mass spectroscopy. The two saponins are new compounds, 3-O-(alpha-L-rhamnopyranosyl (1-->2) beta-D-glucopyranosyl (1-->4) alpha-L-arabinopyranosyl) cyclamiretin A and 3-O-(beta-D-xylopyranosyl) (1-->2) beta-D-glucopyranosyl (1-->4) [beta-D-glucopyranosyl (1-->2)] alpha-L-arabinopyranosyl) cyclamiretin D.
Assuntos
Plantas/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Bolívia , Sequência de Carboidratos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Saponinas/química , Triterpenos/químicaRESUMO
Extracts from leaves and stem bark of Peschiera van heurkii (Muell. Arg.) L. Allorge (syn. Tabernaemontana van heurkii Muell. Arg., Apocynaceae) have been assayed for antileishmanial and antibacterial activities. The activities were concentrated in the alkaloid fractions which yielded 20 indole and bisindole alkaloids. The strongest leishmanicidal and antibacterial activities were observed with the dimeric alkaloids conodurine (1), N-demethylconodurine (= gabunine) (2), and conoduramine (3). Weak toxicity towards macrophage host cells and strong activity against the intracellular amastigote form of Leishmania were observed for compounds 1 and 2. In vivo, 1 was less active than glucantime (= N-methylglucamine antimonate), the drug of reference, while 2 was devoid of activity at 100 mg/kg.
Assuntos
Alcaloides/isolamento & purificação , Antibacterianos/isolamento & purificação , Antiprotozoários/isolamento & purificação , Bactérias/efeitos dos fármacos , Indóis/isolamento & purificação , Leishmania/efeitos dos fármacos , Extratos Vegetais/química , Alcaloides/farmacologia , Animais , Antibacterianos/farmacologia , Antiprotozoários/farmacologia , Indóis/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Leishmania donovani/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Folhas de Planta , Caules de Planta , Relação Estrutura-AtividadeRESUMO
A review of the literature on Alstonia species indicates that evidence in support of their effectiveness in the treatment of malaria is controversial. The antiprotozoal activity of the major alkaloid present in Alstonia species, echitamine, was assessed in vitro against Plasmodium falciparum and Giardia intestinalis. Echitamine displayed little antiplasmodial activity, but two quinoline alkaloids from A. coriacea (corialstonine and corialstonidine) were found to have some activity against P. falciparum although this was approximately 10 times less than that of quinine. None of the three Alstonia alkaloids was active against G. intestinalis. These results are discussed in the context of previously published data.
Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Giardia lamblia/efeitos dos fármacos , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Alcaloides/isolamento & purificação , Animais , Humanos , Extratos Vegetais/farmacologiaRESUMO
Two triterpene saponins have been isolated from the inflorescences of Verbascum nigrum. Their structures were determined by chemical and spectral methods as 3-O-([alpha-L-rhamnosyl-(1-->4)-(beta-D-glucopyranosyl-(1-->3)]-be ta-D-glucopyranosyl]-(1-->2)-beta-fucopyranosyl)-13 beta,28-epoxyolean-11-ene-3 beta,23-diol and 3-O-([alpha-L-rhamnosyl-(1-->4)-(beta-D-glucopyranosyl-(1-->3)-bet a-D- glucopyranosyl]-(1-->2)-beta-fucopyranosyl)-11-methoxy-olean-12-en e-3 beta,23,28-triol.
Assuntos
Plantas Medicinais/química , Saponinas/isolamento & purificação , Sequência de Carboidratos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Estrutura Molecular , Saponinas/químicaRESUMO
Two bioactive saponins were isolated from the stem bark of Petersianthus macrocarpus. Their structures were elucidated by chemical degradations and by a combination of 2D NMR techniques and by Californium plasma desorption mass spectrometry. They are 3-O-([beta-D-galactopyranosyl (1-->2)][beta-D-galactopyranosyl (1-->3)]- beta-D-glucuronopyranosyl)-21-O-[3-(3-tigloyloxynilic acid)-4-tigloyloxy- alpha-L-arabinopyranosyl] barringtogenol C and 3-O-([beta-D-galactopyranosyl (1-->2)][beta-D-galactopyranosyl (1-->3)]-beta-D-glucuronopyranosyl)-28-O-alpha-L-rhamnopyranosyl barringtogenol C-21-O-benzoate. The absolute configuration of nilic acid was determined by partial synthesis. 3,3'-Dimethoxy ellagic acid and 3,3'-dimethoxy-4-O-beta-D- glucopyranosyl ellagic acid were also isolated.