RESUMO
Clinical treatment-failures to affordable drugs encouraged new investigation for discovery and development of new prophylactic and therapeutic interventions against malaria. The Drug Discovery Cluster (DDcl) of the Italian Malaria Network gathers several highly integrated and complementary laboratories from different Italian Institutions to identify, synthesise, screen in vitro and in vivo new antimalarial molecules directed against the intraerythrocytic stage of P. falciparum parasites and/or with transmission blocking activity to select lead compounds for further development. Complementary research activities, both in vitro and in the clinics, aim at investigating the pathogenetic mechanisms of severe malaria anaemia and the different manifestations of the disease in malaria-HIV co-infected patients to identify new therapies and improve survival.
Assuntos
Antimaláricos/farmacologia , Inseticidas/farmacologia , Sociedades Científicas/organização & administração , Animais , Anopheles/efeitos dos fármacos , Anopheles/metabolismo , Anopheles/parasitologia , Antimaláricos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Resistência a Medicamentos , Humanos , Insetos Vetores/efeitos dos fármacos , Insetos Vetores/metabolismo , Insetos Vetores/parasitologia , Inseticidas/uso terapêutico , Itália , Cinurenina/metabolismo , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plasmodium falciparum/efeitos dos fármacosRESUMO
Molluscs of many sorts, which are high in protein and trace minerals, have always been a substantial portion of the human diet. A great variety of mollusc species are therefore of commercial importance throughout the world. Episodes of poisoning occasionally happen to the consumers of molluscs, the main hazard being represented by bivalve molluscs. These organisms are filter-feeders, feeding mainly on a wide range of phytoplankton species. Among the thousands of species of microscopic algae at the base of the marine food chain, there are a few dozen which produce potent toxins. One major category of impact occurs when toxic phytoplankton are filtered from the water as food by shellfish, which then accumulate the algal toxins to levels which can be lethal to humans. Incidences of poisoning related to marine algal toxins come under the main categories of paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), diarrhetic shellfish poisoning (DSP), and amnesic shellfish poisoning (ASP), depending upon the toxins and the symptoms that they cause. Since the beginning of the 1990s, a research program has been initiated to examine the toxin profiles in mussels from the Adriatic Sea. Since then, a number of polyether toxins have been isolated and characterized, some of which represent new additions to the DSP class of biotoxins. During this investigation, new types of toxins have also been isolated. The recent application of LC-MS methods for the detection of Adriatic marine biotoxins made it possible to speed up the analysis of toxic samples.
Assuntos
Bivalves/química , Bivalves/microbiologia , Vetores de Doenças , Doenças Transmitidas por Alimentos/patologia , Toxinas Marinhas/química , Toxinas Marinhas/toxicidade , Fitoplâncton/química , Alimentos Marinhos , Animais , HumanosRESUMO
Sponges [phylum Porifera] are a rich source for the isolation of biologically active and pharmacologically valuable compounds with a high potential to become effective drugs for therapeutic use. However, until now, only one compound has been introduced into clinics because of the limited amounts of starting material available for extraction. To overcome this serious problem in line with the rules for a sustainable use of marine resources, the following routes can be pursued; first, chemical synthesis, second, cultivation of sponges in the sea (mariculture), third, growth of sponge specimens in a bioreactor, and fourth, cultivation of sponge cells in vitro in a bioreactor. The main efforts to follow the latter strategy have been undertaken with the marine sponge Suberites domuncula. This species produces compounds that affect neuronal cells, such as quinolinic acid, a well-known neurotoxin, and phospholipids. A sponge cell culture was established after finding that single sponge cells require cell-cell contact in order to retain their telomerase activity, one prerequisite for continuous cell proliferation. The sponge cell culture system, the primmorphs, comprises proliferating cells that have the potency to differentiate. While improving the medium it was found that, besides growth factors, certain ions (e.g. silicate and iron) are essential. In the presence of silicate several genes required for the formation of the extracellular matrix are expressed (silicatein, collagen and myotrophin). Fe3+ is essential for the synthesis of the spicules, and causes an increased expression of the ferritin-, septin- and scavenger receptor genes. Furthermore, high water current is required for growth and canal formation in the primmorphs. The primmorph system has already been successfully used for the production of pharmacologically useful, bioactive compounds, such as avarol or (2'-5')oligoadenylates. Future strategies to improve the sponge cell culture are discussed; these include the elucidation of those genes which control the proliferation phase and the morphogenesis phase, two developmental phases which the cells in primmorphs undergo. In addition, immortalization of sponge cells by transfection with genomic DNA appears to be a promising way, since recent studies underscore the applicability of this technique for sponges.
Assuntos
Poríferos/metabolismo , Sequência de Aminoácidos , Animais , Reatores Biológicos , Biotecnologia/métodos , Comunicação Celular , Linhagem Celular , Proliferação de Células , Meios de Cultura/metabolismo , DNA/metabolismo , Matriz Extracelular/metabolismo , Imuno-Histoquímica , Ferro/metabolismo , Modelos Químicos , Dados de Sequência Molecular , Neurotoxinas/química , Neurotoxinas/metabolismo , Ácido Quinolínico/química , Homologia de Sequência de Aminoácidos , Sesquiterpenos/química , Fatores de Tempo , TransfecçãoRESUMO
A unique cytotoxic metabolite, turbinamide (1), has been isolated from the marine tunicate Sidnyum turbinatum through a bioassay-guided approach. Its structure has been elucidated by an extensive spectroscopic analysis. Turbinamide demonstrated a strong and selective cytotoxic effect against neuronal cells rather than immune system cells. Structure: see text.
Assuntos
Alcanos/isolamento & purificação , Amidas/isolamento & purificação , Antineoplásicos/isolamento & purificação , Urocordados/química , Alcanos/química , Alcanos/farmacologia , Amidas/química , Amidas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Camundongos , Monócitos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Ratos , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
An investigation of the extracts from bulbs of Allium porrum L. has led to the isolation of four spirostanol saponins. Two of them are new compounds and have been identified as: (25R)-5 alpha-spirostan-3 beta, 6 beta-diol 3-O-{O-beta-D-glucopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1-->3)]-O- beta -D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside} (3) and (25R)-5 alpha-spirostan-3 beta,6 beta-diol 3-O-{O-beta-D-glucopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->2)-O- [beta-D-xylopyranosyl-(1-->3)]-O-beta-D-glucopyranosyl-(1-->4)-beta-D- galactopyranoside} (4). The isolated compounds were evaluated for their antifungal activity.
Assuntos
Allium/química , Saponinas/química , Configuração de Carboidratos , Sequência de Carboidratos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Saponinas/isolamento & purificação , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
A phytochemical investigation of the extracts obtained from bulbs of leek. Allium porrum L. has led to the isolation of five flavonoid glycosides based on the kaempferol aglycone. Two of them are new compounds and have been identified as kaempferol 3-O-[2-O-(trans-3-methoxy-4-hydroxycinnamoyl)-beta-D-galactopyranosyl]-(1-->4)-O-beta-D-glucopyranoside, and kaempferol 3-O-[2-O-(trans-3-methoxy-4-hydroxycinnamoyl)-beta-D-glucopyranosyl]-(1-->6)-O-beta-D-glucopyranoside, on the basis of spectroscopic methods, including 2D NMR. The isolated compounds have been evaluated for their human platelet anti-aggregation activity.
Assuntos
Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Quempferóis , Cebolas/química , Agregação Plaquetária/efeitos dos fármacos , Quercetina/isolamento & purificação , Flavonoides/química , Humanos , Espectroscopia de Ressonância Magnética , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacologiaRESUMO
From wild garlic Allium ursinum three new flavonoid glycosides were identified as kaempferol 3-O-beta-neohesperidoside-7-O-[2-O-(trans-p-coumaroyl)]-beta -D- glucopyranoside, kaempferol 3-O-beta-neohesperidoside-7-O-[2-O-(trans-feruloyl)]-beta-D- glucopyranoside, kaempferol 3-O-beta-neohesperidoside-7-O-[2-O-(trans-p-coumaroyl)-3-O-b eta-D- glucopyranosyl]-beta-D-glucopyranoside and characterized as the peracetates. Additionally, two known flavonoid glycosides kaempferol 3-O-beta-glucopyranoside and kaempferol 3-O-beta-neohesperidoside were isolated. The isolated compounds showed an inhibition of human platelet aggregation.
Assuntos
Flavonoides/química , Flavonoides/farmacologia , Alho/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Plaquetas/efeitos dos fármacos , Sequência de Carboidratos , Flavonoides/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Extratos Vegetais/isolamento & purificação , Inibidores da Agregação Plaquetária/isolamento & purificação , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria UltravioletaRESUMO
An investigation of the extracts from Allium neapolitanum has led to the isolation of 13 flavonoid glycosides, based on kaempferol, quercetin and isorhamnetin. Four of them are new compounds and have been identified as: kaempferol 3-O-[[2-O-alpha-L-rhamnopyranosyl-4-O-beta-D-glucopyranosyl]-beta-D- glucopyranoside]], isorhamnetin 3-O-[[2-O-alpha-L-rhamnopyranosyl-6-O-beta- D-glucopyranosyl]-beta-D-glucopyranoside], isorhamnetin 3-O-[[2-O-alpha-L-rhamnopyranosyl-6-O-beta-D-glycopyranosyl] beta-D-glucopyranoside]-7-O-beta-D-glucopyranoside and isorhamnetin 3-O-[[2-O-alpha-L-rhamnopyranosyl-6-O-beta-D-gentiobiosyl]- beta-D-glucopyranoside]]. The isolated compounds were evaluated for their anti-aggregation human platelet activity.
Assuntos
Allium/química , Flavonoides/química , Flavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Flavonoides/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Itália , Espectroscopia de Ressonância Magnética , Extratos Vegetais/isolamento & purificação , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/isolamento & purificaçãoRESUMO
A clonal culture of Alexandrium andersoni, obtained from germination of a resting cyst, collected from the Gulf of Naples, was found positive for PSP toxicity by mouse bioassay. The toxicity profile of this dinoflagellate consists mainly of toxins belonging to the saxitoxin class, in particular of Saxitoxin (STX) and Neosaxitoxin (NEO), as determined by a wide MS and (1)H NMR analysis. This represents the first report of the presence of A. andersoni in the Mediterranean Sea, as well as of its toxicity.
Assuntos
Dinoflagellida , Saxitoxina/análogos & derivados , Saxitoxina/toxicidade , Animais , Cromatografia em Camada Fina , Dinoflagellida/química , Dinoflagellida/classificação , Itália , Masculino , Mar Mediterrâneo , Camundongos , Saxitoxina/isolamento & purificação , Frutos do Mar/toxicidade , Espectrofotometria UltravioletaRESUMO
This study investigated the composition of diarrhoetic shellfish toxins in the hepatopancreas of mussels from the northern Adriatic Sea. The major toxins were shown to be yessotoxin, identified by its chromatographic properties and spectral data, and okadaic acid, detected both by fluorometric high-performance liquid chromatography and by comparison of its spectral properties with those of an authentic sample.
Assuntos
Bivalves , Éteres Cíclicos/análise , Venenos de Moluscos/química , Oxocinas , Animais , Cromatografia Líquida de Alta Pressão , Éteres Cíclicos/isolamento & purificação , Éteres Cíclicos/toxicidade , Masculino , Mar Mediterrâneo , Camundongos , Venenos de Moluscos/toxicidade , Ácido Okadáico/análiseRESUMO
The diarrhetic shellfish toxin composition in the hepatopancreas of mussels from the northern Adriatic sea was investigated. The major toxins were shown to be yessotoxin (YTX), homoyessotoxin (homoYTX) and 45-hydroxyyessotoxin (45-OHYTX), identified by comparison of their chromatographic and spectral properties with those reported in the literature.
Assuntos
Bivalves/química , Sistema Digestório/química , Éteres Cíclicos/isolamento & purificação , Toxinas Marinhas/isolamento & purificação , Oxocinas , Fitoplâncton/química , Animais , Cromatografia Líquida de Alta Pressão , Itália , Toxinas Marinhas/química , Toxinas Marinhas/classificação , Venenos de Moluscos , Ácido Okadáico/química , Ácido Okadáico/isolamento & purificaçãoRESUMO
In addition to the known (20S,22E)-cholesta-1,4,22-triene-16 beta,18, 20-triol-3-one, (20S,22E)-24-methyl-cholesta-1,4,22-triene-16 beta,18,20-triol-3-one, and (20S,22E)-24-methylcholesta-4,22-diene-16 beta,18,20-triol-3-one, the methanol extract of the Mediterranean anthozoan Antipathes subpinnata was shown to contain five new sterols: (20S,22E)-cholesta-1,4,22-triene-18,20-diol-3-one, (20S,22E)-24-methylcholesta-1,4,22-triene-18,20-diol-3-one, (20S)-cholest-4-ene-16 beta,18,20-triol-3-one, (20S,22E)-cholesta-4,22-diene- 16 beta,18,20-triol-3-one, and (20S,22E)-24-methylcholesta-4,22-diene-16 beta,18,20-triol-3-one, whose stereostructures were elucidated on the basis of physicochemical evidence. The previously unassigned chirality at C-20 of the known sterols has been also established as S.
Assuntos
Cnidários/química , Esteróis/isolamento & purificação , Animais , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Esteróis/químicaRESUMO
The CHCl3 extract of the Mediterranean sponge Clathrina clathrus was shown to contain three new sterols: (22 E)-3 beta-hydroxycholesta-5,8,22-trien-7-one (1), (22 E, 24 xi)-3 beta-hydroxy-24-methylcholesta-5,8,22-trien-7-one (2), and (22 E, 24 xi)-3 beta-hydroxy-24-ethylcholesta-5,8,22-trien-7-one (3), whose structures were elucidated on the basis of physico-chemical evidence.
Assuntos
Colestenos/isolamento & purificação , Colestenonas/isolamento & purificação , Poríferos/análise , Esteróis/isolamento & purificação , Animais , Fenômenos Químicos , Química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrofotometria InfravermelhoRESUMO
Five novel sterols isolated from the marine sponge Oscarella lobularis have been identified on the basis of spectral arguments: cholest-7-ene-3beta,5alpha-diol-6-one (1), cholesta-7,22E-diene-3beta, 5alpha-diol-6-one (2), 24-methylcholesta-7,22E-diene-3beta,5alpha-diol-6-one (3), 24-methylcholesta-7,24(28)-diene-3beta,5alpha-diol-6-one (4), and 24-ethylcholest-7-ene-3beta,5alpha-diol-6-one (5).
Assuntos
Hidroxiesteroides/isolamento & purificação , Cetosteroides/isolamento & purificação , Poríferos/química , Animais , Hidroxiesteroides/química , Cetosteroides/química , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
The sterol composition of the Caribbean sponge Neofibularia nolitangere has been investigated. In addition to usual sterols this sponge elaborates comparable amounts of 24-methylene-4 alpha-methyl-5 alpha-cholest-8-en-3 beta-ol (1), which is very unusual among sponge sterols, and lesser quantities of two new polyoxygenated sterols, (24S)-24-ethyl-5 alpha-cholest-8-ene-5,6 beta,7 alpha-triol (2) and (24S)-24-ethyl-5 alpha-cholest-8(14)-ene-5,6 beta,7 alpha-triol (3).
Assuntos
Poríferos/química , Esteróis/química , Animais , Colestenos/química , Colestenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida/métodos , Hidroxiesteroides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Esteróis/isolamento & purificaçãoRESUMO
The Senegalese sponge Microscleroderma spirophora has been found to produce exclusively very unusual 3 beta-methoxysteroids in place of the common 3 beta-hydroxysteroids. Six different methoxysteroids (three of which are novel compounds) have been isolated and identified by spectroscopic means (MS, IR, 1H and 13C NMR), and their taxonomic significance discussed. A new method for the determination of the configuration at C-24 in saturated 24-ethyl side chains is also proposed.
Assuntos
Poríferos/química , Esteroides/isolamento & purificação , Animais , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Estrutura Molecular , Espectrofotometria Infravermelho , Esteroides/químicaRESUMO
Three novel sterols with a rare D-ring unsaturation were isolated from the marine sponge Topsentia aurantiaca and identified as 5 alpha-cholest-14-ene-3 beta,16 alpha-diol (2), 24R-ethyl-5 alpha-cholest-14-ene-3 beta,16 alpha-diol (3), and 24S-ethyl-5 alpha-cholest-14-ene-3 beta,16 alpha-diol (4). The sponge also elaborates a further D-ring unsaturated sterol, 5 alpha-cholest-15-en-3 beta-ol (1), which has been previously described only as a synthetic product. All the 1H and 13C nuclear magnetic resonances of compounds 1 and 2 were assigned to the relevant protons and carbons by bidimensional COSY, HETCOR, and HMQC nuclear magnetic resonance experiments.
Assuntos
Colestanóis/química , Esteróis/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura MolecularRESUMO
From the fruit body of the fungus Marasmius oreades (family Tricholomataceae), 4,4-dimethyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol (1), probably a biogenetic precursor of ergosterol, has been isolated along with ergosterol. Its stereostructure has been established unequivocally by spectroscopic methods, including 13C nuclear magnetic resonance.
Assuntos
Agaricales/química , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura MolecularRESUMO
The sterol composition of the Caribbean sponge Iotrochota birotulata was investigated. Structure of a new ecdysteroid 2beta,3beta,14alpha, 20beta-tetrahydroxy-22alpha-(2-hydroxyacetiloxy)-5b eta-colest-7-en-6- one (1) was assigned on the basis of spectroscopic and chemical evidence and molecular mechanics calculations. Isolation of the widespread ecdysteroids 2-5 is also reported.
Assuntos
Colestenonas/química , Colestenonas/isolamento & purificação , Poríferos/química , Esteroides/química , Esteroides/isolamento & purificação , Animais , Região do Caribe , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
The sterol composition of the sponge Dysidea fragilis, coming from the lagoon of Venice, has been investigated; our results confirmed the variability of D. fragilis biochemistry. The sponge elaborates, in addition to eight usual 3 beta-hydroxy sterols, thirteen polyhydroxysterols, eight of them (6-13) were novel compounds. Their structures were established by spectroscopic data. New compounds 3 beta,5 alpha,6 beta,7 alpha-tetrahydroxy-cholest-8(9)-en-11-one (8), 3 beta,5 alpha,6 alpha-trihydroxy-9,11-secocholest-7-en-9-one (9) and 3 beta,5 alpha,6 alpha,9 alpha-tetrahydroxy-cholest-7-ene-6-sulfate (11) were proved to be cytotoxic on two different tumor cell lines in vitro.