RESUMEN
The search for active microorganisms for the biotransformation of guttiferone A (1) and C (6) has been successfully undertaken from a collection of endophytic fungi of Symphonia globulifera. Of the twenty-five isolates obtained from the leaves, three are active and have been identified as Bipolaris cactivora. The products obtained are the result of xanthone cyclisation with the formation of two regioisomers among four possible and corresponding to 1,16-oxy-guttiferone and 3,16-oxy-guttiferone. The biotransformation conditions were studied. Interestingly, both oxy-guttiferones A are present in the plant, and the ratio of 3,16-oxy-guttiferone to 1,16-oxy-guttiferone is 4 : 1, very close to that observed by biotransformation (3.8 : 1). These results are consistent with the involvement of endophytes in their formation pathway from guttiferone A, in planta. Finally, biotransformation made it possible to obtain and describe for the first time oxy-guttiferones C.
Asunto(s)
Benzofenonas/metabolismo , Bipolaris/metabolismo , Endófitos/metabolismo , Malpighiales/microbiología , Biotransformación , Malpighiales/química , Hojas de la Planta/química , Hojas de la Planta/microbiologíaRESUMEN
Guttiferone A (GA) 1, a polycyclic polyprenylated acylphloroglucinol (PPAP) isolated from the plant Symphonia globulifera (Clusiaceae), constitutes a novel hit in antimalarial drug discovery. PPAPs do not possess identified biochemical targets in malarial parasites up to now. Towards this aim, we designed and evaluated a natural product-derived photoactivatable probe AZC-GA 5, embedding a photoalkylative fluorogenic motif of the 7-azidocoumarin (AZC) type, devoted to studying the affinity proteins interacting with GA in Plasmodium falciparum. Probe 5 manifested a number of positive functional and biological features, such as (i) inhibitory activity in vitro against P. falciparum blood-stages that was superimposable to that of GA 1, dose-response photoalkylative fluorogenic properties (ii) in model conditions using bovine serum albumin (BSA) as an affinity protein surrogate, (iii) in live P. falciparum-infected erythrocytes, and (iv) in fresh P. falciparum cell lysate. Fluorogenic signals by photoactivated AZC-GA 5 in biological settings were markedly abolished in the presence of excess GA 1 as a competitor, indicating significant pharmacological specificity of the designed molecular probe relative to the native PPAP. These results open the way to identify the detected plasmodial proteins as putative drug targets for the natural product 1 by means of proteomic analysis.
Asunto(s)
Benzofenonas , Colorantes Fluorescentes , Imagen Óptica , Plasmodium falciparum/metabolismo , Proteoma/metabolismo , Proteínas Protozoarias/metabolismo , Benzofenonas/química , Benzofenonas/farmacología , Eritrocitos/parasitología , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Humanos , Plasmodium falciparum/citologíaRESUMEN
Natural products guttiferone A, hyperforin, and aristoforin were able to inhibit or increase SIRT1 catalytic activity, depending on protein concentration and presence of detergent. On the basis of NMR data for guttiferone A, we demonstrated that the aggregation state of the natural product played a crucial role for its interaction with the enzyme. These results are useful to interpret future in vitro structure-activity relationship studies on these natural products in the quest of their biological target(s).
Asunto(s)
Benzofenonas/química , Benzofenonas/farmacología , Productos Biológicos/farmacología , Inhibidores Enzimáticos/farmacología , Sirtuina 1/antagonistas & inhibidores , Benzofenonas/aislamiento & purificación , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Clusiaceae/química , Relación Dosis-Respuesta a Droga , Dispersión Dinámica de Luz , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular , Sirtuina 1/metabolismo , Relación Estructura-ActividadRESUMEN
The aim of this study was to investigate the species Symphonia globulifera, a source of polycyclic polyprenylated acyl phloroglucinols such as guttiferone A, which is known to exhibit a variety of biological activities including noticeable antileishmanial properties. Our goal was the identification and the quantification of guttiferone A in different renewable parts of S. globulifera and its preparative isolation. To the best of our knowledge, there is no data concerning its mechanism of action. Consequently, it is particularly interesting to isolate it in gram quantities in order to establish structure activity relationship studies. After performing high-performance liquid chromatography profiles detecting the presence of guttiferone A and proceeding to its quantification, a centrifugal partition chromatography methodology using a two-phase solvent system of cyclohexane/ethyl acetate/methanol/water (20 :â 1 :â 20 : 1, v/v/v/v) was applied to each extract. In conclusion, a centrifugal partition chromatography system has been developed to ensure a fast, reliable, and scalable way to isolate, with a high level of purity, guttiferone A from five renewable parts of S. globulifera. Moreover, this methodology can be extended to the isolation of other polycyclic polyprenylated acyl phloroglucinols such as guttiferones B, C, and D.
Asunto(s)
Benzofenonas/aislamiento & purificación , Centrifugación por Gradiente de Densidad/métodos , Clusiaceae/química , Benzofenonas/química , Cromatografía Líquida de Alta Presión , Estructura MolecularRESUMEN
Two regioisomeric polycyclic xanthones, 3,16-oxyguttiferone A (2) and 1,16-oxyguttiferone A (3), which are polyprenylated acylphloroglucinol-derived analogues, were isolated from the seeds of Symphonia globulifera, together with their presumed o-dihydroxybenzoyl precursor, guttiferone A (1). Anodic oxidation of 1 into the corresponding o-quinone species proved to be an efficient biomimetic method to generate xanthones 2 and 3 in high overall yield and to confirm their structures. Both compounds displayed cytotoxicity against the HCT 116 colon carcinoma cell line with IC50 values of 8 and 3 µM, respectively.
Asunto(s)
Benzofenonas/aislamiento & purificación , Clusiaceae/química , Xantonas/aislamiento & purificación , Benzofenonas/química , Benzofenonas/farmacología , Guyana Francesa , Células HCT116 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Corteza de la Planta/química , Prenilación , Semillas/química , Estereoisomerismo , Xantonas/químicaRESUMEN
Symphonia globulifera has been widely used in traditional medicine and has therefore been subjected to several phytochemical studies in the American and African continents. Interestingly, some disparities have been observed concerning its metabolic profile. Several phytochemical studies of S. globulifera have led to the identification of more than 40 compounds, including several polycyclic polyprenylated acylphloroglucinols. Biological evaluations have pointed out the promising biological activities of these secondary metabolites, mostly as antiparasitic or antimicrobial, confirming the traditional use of this plant. The purpose of this review is to describe the natural occurrence, botanical aspects, ethnomedicinal use, structure, and biogenesis, as well as biological activities of compounds isolated from this species according to their provenance.
Asunto(s)
Antiinfecciosos/farmacología , Clusiaceae/química , Extractos Vegetales/farmacología , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Vías Biosintéticas , Medicina Tradicional , Metabolómica , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Metabolismo SecundarioRESUMEN
In the last few years, several phytochemical studies have been undertaken on the tropical tree Symphonia globulifera leading to the isolation and characterisation of several compounds exhibiting antiparasitic activities against Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani. The comparative LC-MS based metabolite profiling study conducted on the tree led to the identification of compounds originating from specific tissues. The results showed that renewable organs/tissues can be used as the starting material for the production of polycyclic poly-prenylated-acylphloroglucinols, therefore reducing impacts on biodiversity. This study also underlined the lack of knowledge on the secondary metabolites produced by S. globulifera since only a small number of the total detected features were putatively identified using the database of known compounds for the species.
Asunto(s)
Clusiaceae/química , Bosque Lluvioso , Benzofenonas/química , Bases de Datos Factuales , Flores/química , Guyana Francesa , Metabolómica , Estructura Molecular , Corteza de la Planta/química , Hojas de la Planta/química , Raíces de Plantas/química , Plasmodium falciparum/efectos de los fármacos , Semillas/química , Trypanosoma brucei brucei/efectos de los fármacos , Xantonas/químicaRESUMEN
Hexahomotrioxacalix[3]arenes, commonly called oxacalix[3]arenes, were first reported in 1962. Since then, their chemistry has been expanded to include numerous derivatives and complexes. This review describes the syntheses of the parent compounds, their derivatives, and their complexation behaviour towards cations. Extraction data are presented, as are crystal structures of the macrocycles and their complexes with guest species. Applications in fields as diverse as ion selective electrode modifiers, fluorescence sensors, fullerene separations and biomimetic chemistry are described.