RESUMEN
Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (-)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (-)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (-)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (-)-mucosin (1) is also presented.
Asunto(s)
Productos Biológicos , Compuestos Bicíclicos Heterocíclicos con Puentes , Productos Biológicos/química , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Modelos Moleculares , EstereoisomerismoRESUMEN
The immunomodulating effects of isolated proanthocyanidin-rich fractions, procyanidins C1, B5 and B2 and anthocyanins of Aronia melanocarpa were investigated. In this work, the complement-modulating activities, the inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages and effects on cell viability of these polyphenols were studied. Several of the proanthocyanidin-rich fractions, the procyanidins C1, B5 and B2 and the cyanidin aglycone possessed strong complement-fixing activities. Cyanidin 3-glucoside possessed stronger activity than the other anthocyanins. Procyanidins C1, B5 and B2 and proanthocyanidin-rich fractions having an average degree of polymerization (PD) of 7 and 34 showed inhibitory activities on NO production in LPS-stimulated RAW 264.7 mouse macrophages. All, except for the fraction containing proanthocyanidins with PD 34, showed inhibitory effects without affecting cell viability. This study suggests that polyphenolic compounds of A. melanocarpa may have beneficial effects as immunomodulators and anti-inflammatory agents.
Asunto(s)
Factores Inmunológicos/farmacología , Photinia/química , Polifenoles/farmacología , Animales , Antocianinas/química , Antocianinas/farmacología , Factores Inmunológicos/química , Activación de Macrófagos , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/metabolismo , Polifenoles/química , Proantocianidinas/química , Proantocianidinas/farmacologíaRESUMEN
The olon tree, Zanthoxylum heitzii (syn. Fagara heitzii) is commonly found in the central-west African forests. In the Republic of Congo (Congo-Brazzaville) its bark is anecdotally reported to provide human protection against fleas. Here we assess the insecticidal activities of Z. heitzii stem bark, seed and leaf extracts against Anopheles gambiae s.s, the main malaria vector in Africa. Extracts were obtained by Accelerated Solvent Extraction (ASE) using solvents of different polarity and by classical Soxhlet extraction using hexane as solvent. The insecticidal effects of the crude extracts were evaluated using topical applications of insecticides on mosquitoes of a susceptible reference strain (Kisumu [Kis]), a strain homozygous for the L1014F kdr mutation (kdrKis), and a strain homozygous for the G119S Ace1R allele (AcerKis). The insecticidal activities were measured using LD50 and LD95 and active extracts were characterized by NMR spectroscopy and HPLC chromatography. Results show that the ASE hexane stem bark extract was the most effective compound against An. gambiae (LD50 = 102 ng/mg female), but was not as effective as common synthetic insecticides. Overall, there was no significant difference between the responses of the three mosquito strains to Z. heitzii extracts, indicating no cross resistance with conventional pesticides.
Asunto(s)
Anopheles/efectos de los fármacos , Insectos Vectores/efectos de los fármacos , Insecticidas/farmacología , Corteza de la Planta/química , Extractos Vegetales/farmacología , Animales , Femenino , Insecticidas/aislamiento & purificación , Dosificación Letal Mediana , Control de Mosquitos , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Semillas/química , Zanthoxylum/químicaRESUMEN
Plants used in traditional medicine in the management of epilepsy could potentially yield novel drug compounds with antiepileptic properties. The medicinal plant Securidaca longepedunculata is widely used in traditional medicine in the African continent, and epilepsy is among several indications. Limited knowledge is available on its toxicity and medicinal effects, such as anticonvulsant activities. This study explores the potential in vivo inhibition of seizure-like paroxysms and toxicity effects of dichloromethane (DCM) and ethanol (EtOH) extracts, as well as isolated xanthones and benzoates of S. longepedunculata. Ten phenolic compounds were isolated from the DCM extract. All of the substances were identified by nuclear magnetic resonance spectroscopy. Assays for toxicity and inhibition of pentylenetetrazole (PTZ)-induced seizure-like paroxysms were performed in zebrafish larvae. Among the compounds assessed in the assay for maximum tolerated concentration (MTC), benzyl-2-hydroxy-6-methoxy-benzoate (MTC 12.5 µM), 4,8-dihydroxy-1,2,3,5,6-pentamethoxyxanthone (MTC 25 µM), and 1,7-dihydroxy-4-methoxyxanthone (MTC 6.25 µM) were the most toxic. The DCM extract, 1,7-dihydroxy-4-methoxyxanthone and 2-hydroxy-1,7-dimethoxyxanthone displayed the most significant inhibition of paroxysms by altering the locomotor behavior in GABAA receptor antagonist, PTZ, which induced seizures in larval zebrafish. The EtOH extract, benzyl benzoate, and benzyl-2-hydroxy-6-methoxy-benzoate unexpectedly increased locomotor activity in treated larval zebrafish and decreased locomotor activity in nontreated larval zebrafish, seemingly due to paradoxical excitation. The results reveal promising medicinal activities of this plant, contributing to our understanding of its use as an antiepileptic drug. It also shows us the presence of potentially new lead compounds for future drug development.
Asunto(s)
Epilepsia , Securidaca , Animales , Pez Cebra , Securidaca/química , Convulsiones/tratamiento farmacológico , Anticonvulsivantes/farmacología , Epilepsia/tratamiento farmacológico , Extractos Vegetales/química , Pentilenotetrazol , Benzoatos/efectos adversosRESUMEN
Extracts, subfractions, isolated anthocyanins and procyanidins, and two phenolic acids from aronia [Aronia melanocarpa] were investigated for their CYP3A4 inhibitory effects, using midazolam as the probe substrate and recombinant insect cell microsomes expressing CYP3A4 as the enzyme source. Procyanidin B5 was a considerably stronger CYP3A4 inhibitor in vitro than the isomeric procyanidin B2 and comparable to bergamottin, a known CYP3A4 inhibitor from grapefruit juice. The inhibitory activity of proanthocyanidin-containing fractions was correlated to the degree of polymerization. Among the anthocyanins, cyanidin 3-arabinoside showed stronger CYP3A4 inhibition than cyanidin 3-galactoside and cyanidin 3-glucoside. Thus, the ability to inhibit CYP3A4 in vitro seems to be influenced by the sugar unit linked to the anthocyanidin.
Asunto(s)
Antocianinas/farmacología , Inhibidores del Citocromo P-450 CYP3A , Hidroxibenzoatos/farmacología , Photinia/química , Proantocianidinas/farmacología , Animales , Antocianinas/química , Antocianinas/aislamiento & purificación , Biflavonoides/química , Biflavonoides/aislamiento & purificación , Biflavonoides/farmacología , Catequina/química , Catequina/aislamiento & purificación , Catequina/farmacología , Citocromo P-450 CYP3A , Frutas/química , Furocumarinas/farmacología , Glicosilación , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/aislamiento & purificación , Concentración 50 Inhibidora , Insectos , Microsomas , Midazolam/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Proantocianidinas/química , Proantocianidinas/aislamiento & purificaciónRESUMEN
Many bacteria growing on surfaces form biofilms. Adaptive and genetic changes of the microorganisms in this structure make them resistant to antimicrobial agents. Biofilm-forming organisms on medical devices can pose serious threats to human health. Thus, there is a need for novel prevention and treatment strategies. This study aimed to evaluate the ability of Aronia melanocarpa extracts, subfractions and compounds to prevent biofilm formation and to inhibit bacterial growth of Escherichia coli and Bacillus cereus in vitro. It was found that several aronia substances possessed anti-biofilm activity, however, they were not toxic to the species screened. This non-toxic inhibition may confer a lower potential for resistance development compared to conventional antimicrobials.
Asunto(s)
Bacillus cereus/efectos de los fármacos , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Photinia/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Bacillus cereus/fisiología , Escherichia coli/fisiología , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Extracts, subfractions, isolated anthocyanins and isolated procyanidins B2, B5 and C1 from the berries and bark of Aronia melanocarpa were investigated for their antioxidant and enzyme inhibitory activities. Four different bioassays were used, namely scavenging of the diphenylpicrylhydrazyl (DPPH) radical, inhibition of 15-lipoxygenase (15-LO), inhibition of xanthine oxidase (XO) and inhibition of α-glucosidase. Among the anthocyanins, cyanidin 3-arabinoside possessed the strongest and cyanidin 3-xyloside the weakest radical scavenging and enzyme inhibitory activity. These effects seem to be influenced by the sugar units linked to the anthocyanidin. Subfractions enriched in procyanidins were found to be potent α-glucosidase inhibitors; they possessed high radical scavenging properties, strong inhibitory activity towards 15-LO and moderate inhibitory activity towards XO. Trimeric procyanidin C1 showed higher activity in the biological assays compared to the dimeric procyanidins B2 and B5. This study suggests that different polyphenolic compounds of A. melanocarpa can have beneficial effects in reducing blood glucose levels due to inhibition of α-glucosidase and may have a potential to alleviate oxidative stress.
Asunto(s)
Antocianinas/farmacología , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Photinia/química , Extractos Vegetales/farmacología , Antocianinas/química , Inhibidores Enzimáticos/química , Frutas/química , Estructura Molecular , Corteza de la Planta/química , Extractos Vegetales/química , Proantocianidinas/química , Proantocianidinas/farmacologíaRESUMEN
Diarrhoea is a common disease which causes pain and may be deadly, especially in developing countries. In Bangladesh, diarrhoeal diseases affect thousands of people every year, and children are especially vulnerable. Bacterial toxins or viral infections are the most common cause of the disease. The diarrhoea outbreaks are often associated with flood affected areas with contaminated drinking water and an increased risk of spreading the water-borne disease. Not surprisingly, plants found in the near surroundings have been taken into use by the local community as medicine to treat diarrhoeal symptoms. These plants are cheaper and more easily available than conventional medicine. Our question is: What is the level of documentation supporting the use of these plants against diarrhoea and is their consumption safe? Do any of these plants have potential for further exploration? In this review, we have choosen seven plant species that are used in the treatment of diarrhoea; Diospyros peregrina, Heritiera littoralis, Ixora coccinea, Pongamia pinnata, Rhizophora mucronata, Xylocarpus granatum, and Xylocarpus moluccensis. Appearance and geographical distribution, traditional uses, chemical composition, and biological studies related to antidiarrhoeal activity will be presented. This review reveals that there is limited scientific evidence supporting the traditional use of these plants. Most promising are the barks from D. peregrina, X. granatum and X. moluccensis which contain tannins and have shown promising results in antidiarrhoeal mice models. The leaves of P. pinnata also show potential. We suggest these plants should be exploited further as possible traditional herbal remedies against diarrhoea including studies on efficacy, optimal dosage and safety.
Asunto(s)
Diarrea/tratamiento farmacológico , Magnoliopsida/química , Medicina Tradicional , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Plantas Medicinales/química , Animales , Bangladesh , Diospyros , Humanos , Meliaceae , Millettia , Taninos/uso terapéuticoRESUMEN
In Malian traditional medicine the roots of Cochlospermum tinctorium are used in the treatment of gastric ulcer, but extending harvesting is causing a growing concern of a dramatic reduction in the wild plant population. In the present study cultivation of C. tinctorium is evaluated, and structural components and bioactive properties of crude water extracts and isolated polysaccharide fractions from roots of wild and cultivated C. tinctorium are compared. The crude water extracts were shown to contain starch, pectin- and inulin-type polysaccharides, in addition to phenolic substances and protein, while the isolated acidic polysaccharide fractions contained mainly monosaccharides typical for pectins. The monosaccharide compositions of the polysaccharide fractions from roots of wild versus cultivated plants were comparable, albeit the yields in the cultivated roots were lower. Furthermore, the crude extracts and isolated polysaccharide fractions from wild and cultivated roots exhibited similar complement fixating activities, but were not able to activate macrophages. The crude extracts from cultivated roots were also shown to be moderate radical scavengers. The present study has shown that roots of cultivated C. tinctorium contain the same types of bioactive polysaccharides as the wild roots. However, in order to utilize roots of cultivated C. tinctorium in traditional medicine the cultivation method should be improved.
Asunto(s)
Bixaceae/química , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Raíces de Plantas/química , Polisacáridos/farmacología , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Ratones , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Relación Estructura-Actividad , Agua/químicaRESUMEN
The ethanol extract of roots of Solidago canadensis yielded eight labdane-type diterpenes. Five of those were new natural compounds (9,13,15,16-bisepoxy-labdane-7-ene-6,15-dione (3a), 13-epi-9,13,15,16-bisepoxy-labdane-7-ene-6,15-dione (3b), 15,16-epoxy-labdane-7,13-diene-6,16-dione (5), 15-ethoxy-9,13,15,16-bisepoxy-labdane-7-ene-6-one (6a) and 13-epi-15-ethoxy-9,13,15,16-bisepoxy-labdane-7-ene-6-one (6b). The known labdane diterpenes deoxysolidagenone (1), solidagenone (2) and 15,16-epoxy-labdane-7,13-diene-6,15-dione (4) were also isolated. Chemical structures were determined using 1D and 2D NMR techniques and MS analysis.
Asunto(s)
Asteraceae/química , Diterpenos/química , Solidago/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Verbascoside and isoverbascoside, present at 0.7% and 0.2% (w/w dryweight), were identified to be major compounds that could contribute to the metal complexation in Blepharis aspera collected in Botswana, Africa. The metallophyte B. aspera has high ability to cope with a high level of metal accumulation. The presence of metal complexing compounds and/or antioxidants can prevent oxidative reactions in lipids, proteins and DNA that take place due to the metal accumulation. On-line liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) was applied for the identification, while electrospray-mass spectrometry (ESI-MS) and UV-vis spectroscopy was used to assess whether these compounds can complex with metals. It was found that verbascoside and isoverbascoside may form complexes with nickel, iron (verbascoside only) and copper. Thus, the presence of verbascoside and isoverbascoside can explain the survival of B. aspera in mineral-rich areas.
Asunto(s)
Acanthaceae/química , Glucósidos/aislamiento & purificación , Fenoles/aislamiento & purificación , Cobre/química , Flores/química , Glucósidos/química , Hierro/química , Níquel/química , Fenoles/química , Hojas de la Planta/química , Tallos de la Planta/químicaRESUMEN
15-lipoxygenase (15-LO) has been implicated in oxidation of low-density lipoproteins (LDL), a process believed to be important for the development of atherosclerosis, as well as other pathogenic conditions. Potent and selective inhibitors of 15-LO may have a drug potential. In this study, purines with a variety of substituents have been examined as inhibitors of 15-lipoxygenase (15-LO) from soybeans. Several 6-substitued purines where the purine ring and a phenyl ring in the substituent were separated by a "spacer" were synthesized and their ability to inhibit the enzyme was explored. Sepa ration of the purine and the phenyl rings with none, one or two sp3-carbons resulted in essentially inactive compounds, trans-styrylpurines and phenylethynylpurines, on the other hand, they exhibited activity close to the well-known 15-LO inhibitor quercetin. High activity was also found when the "spacer" was a trans-cyclopropyl ring. The shape of the spacer was important; a corresponding cis-cyclopropylpurine exhibited much less affinity for the enzyme. Only minor differences in inhibitory activity against 15-LO were found regardless of whether an N-substituent was situated on N-9 or N-7, even when the N-substituent was relatively large. Also, a variety of substituents in the purine 2- and 8-position were well tolerated.
Asunto(s)
Araquidonato 15-Lipooxigenasa/metabolismo , Inhibidores de la Lipooxigenasa/síntesis química , Inhibidores de la Lipooxigenasa/farmacología , Purinas/síntesis química , Purinas/farmacología , Relación Estructura-ActividadRESUMEN
A number of indolizine 1-sulfonates have been prepared by cyclization of cyclopropenones with pyridines followed by trapping of the intermediate 1-indolizinol with a sulfonyl halide, and examined as inhibitors of 15-lipoxygenase (15-LO). The compounds display IC(50) values between 15 and 42 microM; all are more active than the well-known 15-LO inhibitor quercetin (IC(50) 51 microM). A wide variety of substituents are well tolerated. The enzyme inhibition was not affected by preincubation or the presence of a detergent and no significant particle formation was observed. Hence, inhibition from aggregates of indolizines, promiscuous inhibition, is highly unlikely.
Asunto(s)
Arilsulfonatos/farmacología , Inhibidores Enzimáticos/farmacología , Glycine max/enzimología , Indolizinas/farmacología , Inhibidores de la Lipooxigenasa , Arilsulfonatos/síntesis química , Inhibidores Enzimáticos/síntesis química , Indolizinas/síntesis químicaRESUMEN
Synthetic cytokinin analogues as well as the well known CKs 6-benzylaminopurine (BAP), kinetin and trans-zeatin were examined for antioxidant activity. The compounds were tested as potential diphenylpicrylhydrazyl (DPPH) scavengers and as inhibitors of 15-lipoxygenase (15-LO). The natural plant hormones were essentially inactive in both assays, but several synthetic analogues have a profound inhibiting effect on 15-lipoxygenase from soybeans. The same compounds were only weak DPPH scavengers and they may therefore be regarded as so-called non antioxidant inhibitors of 15-LO.
Asunto(s)
Antioxidantes/síntesis química , Citocininas/síntesis química , Inhibidores de la Lipooxigenasa , Purinas/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Citocininas/química , Citocininas/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Purinas/química , Purinas/farmacología , Glycine max/enzimología , Relación Estructura-ActividadRESUMEN
15-Lipoxygenase (15-LO) has been implicated in oxidation of low-density lipoproteins (LDL) and this enzyme may be involved in the development of atherosclerosis. We have examined 1-substituted indolizines as possible inhibitors of 15-LO from soy beans and from rabbit reticulocytes. Most compounds studied were significantly more active as inhibitors of 15-LO from soy beans than quercetin. The indolizines were slightly less potent inhibitors of the mammalian enzyme, but we found good correlation between inhibitory activity against both 15-LO enzymes studied. Several of the compounds were only weak DPPH scavengers and they may therefore be regarded as so-called non antioxidant inhibitors of 15-LO.