Química de Productos Naturales y Sintéticos Bioactivos

Química de Productos Naturales Marinos

Los organismos marinos constituyen una importante fuente de productos naturales con características estructurales singulares y con un enorme potencial para su aplicación en la industria biomédica, agroquímica y cosmética

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Fondo 1
Presentación

La investigación que se desarrolla en el grupo de Química de Productos Naturales Marinos del IPNA tiene como principal objetivo el descubrimiento de nuevas moléculas de macroorganismos y microorganismos marinos y estudiar su potencial terapéutico.

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esquema
Macroorganismos marinos

La producción de metabolitos secundarios es dependiente del hábitat, por lo que una parte de nuestro trabajo se centra en el estudio de algas, esponjas, moluscos, corales,… procedentes de diversos hábitats tales como: Panamá, Chile, Antártida y Canarias.

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Mapa
Microorganismos marinos

Los microorganismos marinos han desarrollado mecanismos fisiológicos y bioquímicos únicos para sobrevivir en hábitats extremos y altamente competitivos produciendo metabolitos secundarios únicos y con alto valor terapéutico. Otra de nuestras líneas de investigación consiste en el estudio bioguiado de productos naturales producidos por hongos, bacterias y actinomicetos procedentes de muestras de sedimentos marinos.

Activación de rutas metabólicas silentes de actinomicetos marinos Una parte de nuestros esfuerzos se centra en la activación de rutas no expresadas del metabolismo secundario de nuestra colección de actinomicetos marinos con el fin de estimular la producción de nuevos compuestos susceptibles de convertirse en potenciales agentes terapéuticos o herramientas biológicas.

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Esquema
Determinación de la actividad biológica de extractos y de compuestos puros
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Lab

El potencial terapéutico e interés industrial de los extractos y productos puros se establece a través de los ensayos de actividad antibacteriana y antifúngica que realizamos en el laboratorio y mediante colaboraciones con otros grupos de investigación y con empresas.

Publicaciones destacadas

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Chloro-Furanocembranolides from Leptogorgia

Chloro-Furanocembranolides from Leptogorgia sp. Improve Pancreatic Beta-Cell Proliferation

Two new chloro-furanocembranolides (1, 2) and two new 1,4-diketo cembranolides (3, 4) were isolated from the crude extract of Leptogorgia sp. together with a new seco-furanocembranolide (5) and the known Z-deoxypukalide (6), rubifolide (7), scabrolide D (8) and epoxylophodione (9). Their structures were determined based on spectroscopic evidence. Four compounds: 1, 2, 7 and 8 were found to activate the proliferation of pancreatic insulin-producing (beta) cells.

Gallardo, Amalia; Díaz-Marrero, Ana R. ; Rosa, José M. de la ; D'Croz, Luis; Perdomo, Germán; Cózar-Castellano, Irene; Darias, Jose; Cueto, Mercedes

Marine Drugs 16(2): 49 (2018)
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A set of biogenetically interesting polyhalogenated

A set of biogenetically interesting polyhalogenated acetogenins from Ptilonia magellanica

Ptilonines A−F, pyranosylmagellanicus D−E and magellenediol are previously undescribed acetogenins isolated from the red alga Ptilonia magellanica. Their structures were determined from spectroscopic evidence. The absolute configuration of the known pyranosylmagellanicus A, was established by derivatization with (R)− and (S)−α−methoxy −α−phenylacetic acids (MPA). Ptilonines exhibit an unusual halogenation pattern, that may confer evolutionary advantages to Ptilonia magellanica, for which a biogenetic origin is proposed. The antimicrobial effect of some of these compounds was evaluated.

Gallardo, Amalia; Cueto, Mercedes; Díaz-Marrero, Ana R. ; Rosa, José M. de la; Fajardo, Víctor; San-Martín, Aurelio,; Darias, José 

Phytochemistry 145: 111-120 (2018)
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Leptolide Improves Insulin Resistance

Leptolide Improves Insulin Resistance in Diet-Induced Obese Mice

Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity. To this end, we tested the hypothesis that leptolide should protect against fatty acid-induced insulin resistance in hepatocytes. In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two-fold above vehicle-treated HepG2 cells. In addition, leptolide (0.1 µM) counteracted palmitate-induced insulin resistance by augmenting by four-fold insulin-stimulated phosphorylation of PKB in HepG2 cells. In vivo, acute intraperitoneal administration of leptolide (0.1 mg/kg and 1 mg/kg) improved glucose tolerance and insulin sensitivity in lean mice. Likewise, prolonged leptolide treatment (0.1 mg/kg) in diet-induced obese mice improved insulin sensitivity. These effects were paralleled with an ~50% increased of insulin-stimulated phosphorylation of PKB in liver and skeletal muscle and reduced circulating pro-inflammatory cytokines in obese mice. We concluded that leptolide significantly improves insulin sensitivity in vitro and in obese mice, suggesting that leptolide may be another potential treatment for T2DM

Villa-Pérez, Pablo; Cueto, Mercedes; Díaz-Marrero, Ana R; Lobatón, Carmen D.; Moreno, Alfredo; Perdomo, Germán; Cózar-Castellano, Irene

Marine Drugs 15(9): 2889 (2017)
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The Polyphenol Altenusin Inhibits in Vitro Fibrillization

The polyphenol altenusin inhibits in vitro fibrillization of tau and reduces induced tau pathology in primary neurons

In Alzheimer’s disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.

Chua, Sook Wern; Cornejo, Alberto; Eersel, Janet van; Stevens, Claire H.; Vaca, Inmaculada; Cueto, Mercedes; Kassiou, Michael; Gladbach, Amadeus; Macmillan, Alex; Lewis, Lev; Whan, Renee; Ittner, Lars M.

ACS Chemical Neuroscience 8(4): 743-751 (2017)
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Oxysterols from an octocoral of the genus Gorgonia

Oxysterols from an octocoral of the genus Gorgonia from the eastern Pacific of Panama

Eighteen new oxysterols have been isolated from a previously undescribed octocoral collected from the eastern Pacific of Panama. Their structures were determined based on spectroscopic evidence. The absolute configuration was established by derivatization with (R)- and (S)-MPA. Antimicrobial and antileishmanial effects were evaluated.

Cardoso-Martínez, F.; Rosa, José M. de la ; Díaz-Marrero, Ana R.; Darias, José; D'Croz, Luis; Jiménez-Antón, M. Dolores; Corral, María Jesús; García, Rocío; Alunda Rodríguez, Jose María; Cueto, Mercedes

RSC Advances 6: 38579-38591 (2016)
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Tanzawaic acids isolated from a marine-derived fungus

Tanzawaic acids isolated from a marine-derived fungus of the genus Penicillium with cytotoxic activities

Tanzawaic acids M (1), N (2), O (3) and P (4) and the known tanzawaic acids B (5) and E (6), have been isolated from an extract of a cultured marine-derived fungus (strain CF07370) identified as a member of the genus Penicillium. The structures of 1–4 were determined based on spectroscopic evidence. The antimicrobial and cytotoxic activities of compounds 1–6 were evaluated.

Cardoso-Martínez, F.; Rosa, José M. de la; Díaz-Marrero, Ana R.; Darias, José; Cerella, Claudia; Diederich, Marc; Cueto, Mercedes

Organic and Biomolecular Chemistry 13(26): 7248-7256 (2015)

Otros grupos de investigación

Química de Productos Naturales y Sintéticos Bioactivos

Química de Productos Naturales y Sintéticos Bioactivos