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BACKGROUND: According to the WHO, 12 bacteria cause numerous human infections, including Enterobacteriaceae Klebsiella pneumoniae, and thus represent a public health problem. Microbial resistance is associated with biofilm formation; therefore, it is critical to know the biofilm-inducing potential of various compounds of everyday life. Likewise, the reversibility of biofilms and the modulation of persister cells are important for controlling microbial pathogens. In this work, we investigated the biofilm-inducing effects of xanthones from Garcinia mangostana on Klebsiella pneumoniae. Furthermore, we investigated the reversal effect of 3-methyl-2(5H)-furanone and the formation of persister cells induced by xanthones and their role in modulating the biofilm to the antibiotic gentamicin. METHODS: To analyze the biofilm-inducing role of xanthones from Garcinia mangostana, cultures of K. pneumoniae containing duodenal probe pieces were treated with 0.1-0.001 µM α- and γ-mangostin, and the biofilm levels were measured using spectrophotometry. To determine biofilm reversion, cultures treated with xanthones, or gentamicin were mixed with 3-methyl-2(5H)-furanone or N-butyryl-DL-homoserine lactone. The presence of K. pneumoniae persister cells was determined by applying the compounds to the mature biofilm, and the number of colony-forming units was counted. RESULTS: The xanthones α- and γ-mangostin increased K. pneumoniae biofilm production by 40% with duodenal probes. However, 3-methyl-2(5H)-furanone at 0.001 µΜ reversed biofilm formation by up to 60%. Moreover, adding the same to a culture treated with gentamicin reduced the biofilm by 80.5%. This effect was highlighted when 3-methyl-2(5H)-furanone was administered 6 h later than xanthones. At high concentrations of α-mangostin, persister K. pneumoniae cells in the biofilm were about 5 - 10 times more abundant than cells, whereas, with γ-mangostin, they were about 100 times more. CONCLUSION: Two xanthones, α- and γ-mangostin from G. mangostana, induced biofilm formation in K. pneumoniae and promoted persister cells. However, the biofilm formation was reversed by adding 3-methyl-2(5H)-furanone, and even this effect was achieved with gentamicin. In addition, this compound controlled the persister K. pneumoniae cells promoted by α-mangostin. Thus, synthetic, and natural biofilm-inducing compounds could harm human health. Therefore, avoiding these substances and looking for biofilm inhibitors would be a strategy to overcome microbial resistance and recover antibiotics that are no longer used.
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Garcinia mangostana , Xantonas , Humanos , Lactonas , Antibacterianos/farmacologia , Biofilmes , Gentamicinas , Serina , Xantonas/farmacologiaRESUMO
Current antidiabetic drugs have severe side effects, which may be minimized by new selective molecules that strongly inhibit α-glucosidase and weakly inhibit α-amylase. We have synthesized novel alkoxy-substituted xanthones and imidazole-substituted xanthones and have evaluated them for their in silico and in vitro α-glucosidase and α-amylase inhibition activity. Compounds 6c, 6e, and 9b promoted higher α-glucosidase inhibition (IC50 = 16.0, 12.8, and 4.0 µM, respectively) and lower α-amylase inhibition (IC50 = 76.7, 68.1, and >200 µM, respectively) compared to acarbose (IC50 = 306.7 µM for α-glucosidase and 20.0 µM for α-amylase). Contrarily, derivatives 10c and 10f showed higher α-amylase inhibition (IC50 = 5.4 and 8.7 µM, respectively) and lower α-glucosidase inhibition (IC50 = 232.7 and 145.2 µM, respectively). According to the structure-activity relationship, attaching 4-bromobutoxy or 4'-chlorophenylacetophenone moieties to the 2-hydroxy group of xanthone provides higher α-glucosidase inhibition and lower α-amylase inhibition. In silico studies suggest that these scaffolds are key in the activity and interaction of xanthone derivatives. Enzymatic kinetics studies showed that 6c, 9b, and 10c are mainly mixed inhibitors on α-glucosidase and α-amylase. In addition, drug prediction and ADMET studies support that compounds 6c, 9b, and 10c are candidates with antidiabetic potential.
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Inibidores de Glicosídeo Hidrolases , Xantonas , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , alfa-Amilases , Hipoglicemiantes/farmacologia , Relação Estrutura-Atividade , Imidazóis/farmacologia , Xantonas/farmacologia , Estrutura MolecularRESUMO
Eriocaulaceae is a pantropical family whose main center of biodiversity is in Brazil. In general, the family has about 1200 species, in which phytochemical and biological studies have shown a variety of structures and activities. The aim of this research is to compile the compounds isolated in the Eriocaulaceae family and carry out a computational study on their biological targets. The bibliographic research was carried out on six databases. Tables were built and organized according to the chemical class. In addition, a summary of the methods of isolating the compounds was also made. In the computational study were used ChEMBL platform, DRAGON 7.0, and the KNIME 4.4.0 software. Two hundred and twenty-two different compounds have been isolated in sixty-eight species, divided mainly into flavonoids and naphthopyranones, and minor compounds. The ligand-based virtual screening found promising molecules and molecules with multitarget potential, such as xanthones 194, 196, 200 and saponin 202, with xanthone 194 as the most promising. Several compounds with biological activities were isolated in the family, but the chemical profiles of many species are still unknown. The selected structures are a starting point for further studies to develop new antiparasitic and antiviral compounds based on natural products.
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Eriocaulaceae , Eriocaulaceae/química , Flavonoides/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Aprendizado de MáquinaRESUMO
Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. Garcinia mangostana is an interesting species because there have been identified xanthones with the potential to inhibit these enzymes. In this study, the multitarget inhibitory potential of xanthones from G. mangostana against AA, AG and PL was assessed. The methodology included the isolation and identification of bioactive xanthones, the synthesis of some derivatives and a molecular docking study. The chemical study allowed the isolation of five xanthones (1-5). Six derivatives (6-11) were synthesized from the major compound, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle. Compounds with multitarget activity correspond to 2, 4, 5, 6 and 9, highlighting 6 with IC50 values of 33.3 µM on AA, 69.2 µM on AG and 164.4 µM on PL. Enzymatic kinetics and molecular docking studies showed that the bioactive xanthones are mainly competitive inhibitors on AA, mixed inhibitors on AG and non-competitive inhibitors on PL. The molecular coupling study established that the presence of methoxy, hydroxyl and carbonyl groups are important in the activity and interaction of polyfunctional xanthones, highlighting their importance depending on the mode of inhibition.
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Diabetes Mellitus Tipo 2 , Garcinia mangostana , Xantonas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Garcinia mangostana/química , Lipase , Simulação de Acoplamento Molecular , Xantonas/química , alfa-Amilases , alfa-GlucosidasesRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The tribe Symphonieae (Clusiaceae) encompasses 48 species accommodated in seven genera (Lorostemon, Montrouziera, Moronobea, Pentadesma, Platonia, Symphonia and Thysanostemon). Parts of these plants, mainly the exudates and the seeds oil are useful for different purposes, especially for treating dermatological conditions. In addition to the role in the folk medicine, some species are of great economic and cultural importance for native people from different continents. AIM OF THE REVIEW: The goal of this review is to critically summarize the current knowledge on systematics, ethnobotanical, chemical and pharmacological aspects of species from the tribe Symphonieae, as well as to provide support for future taxonomic and phylogenetic studies on the Clusiaceae family. MATERIALS AND METHODS: The available information was gathered from many different databases (Web of Science, ScienceDirect, Scopus, Pubmed, ChemSpider, SciFinder, ACS Publications, Wiley Online Library, Useful Tropical Plants Database, Google Scholar). Additional data from books, theses and dissertations were also included in this review. RESULTS: Chemical studies of Symphonieae have demonstrated that the genera are a source of benzophenones, xanthones and biflavonoids. Components as sesquiterpenoids, triterpenoids, flavonoids, free fatty acids, among others, have also been reported. Extracts and compounds isolated from a variety of species have been exhibiting antimicrobial, cytotoxic and antiprotozoal activities, corroborating part of their medicinal uses. In addition, certain species produce edible fruits and a kind of "butter" with economic importance. All species produce exudate, which often has great relevance in the daily lives of local people. CONCLUSION: Several species of Symphonieae have potential therapeutic applications and some of them have been investigated to scientifically validate their popular uses. In addition, a number of species have proved to be a rich source of promising pharmacologically active compounds. Finally, the value of fruits, exudate and butter, for instance, should serve as a stimulus for the sustainable development of products that aim to take advantage of these natural resources.
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Clusiaceae/química , Medicina Tradicional/métodos , Extratos Vegetais/farmacologia , Animais , Etnobotânica , Etnofarmacologia , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/químicaRESUMO
This work aimed to carry out phytochemical prospecting and evaluate the antioxidant potential of Diplopterys pubipetala, a species of Malpighiaceae family that has not yet been studied.In qualitative analyses of hydroethanolic extracts of leaves and stems were detected the presence of flavonoids, alkaloidsand terpenes. The histochemical evaluation evidenced a greater distribution of these compounds in the tissues of leaf when compared with those of stem. The analysis by mass spectrometry allowed the identification of prenylated xanthones and glycoside flavonoids that have not yet been reported in the literature. The antioxidant activity of the stem extract was considered moderate (IAA = 0.79), but the leaves presented a strong antioxidant activity (IAA = 1.6). In this work we present information about the phytochemicals of D. pubipetala, showing that the species is promising in obtaining compounds with medicinal potential mainly antioxidant potential.
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Malpighiaceae , Antioxidantes/química , Flavonoides/química , Malpighiaceae/química , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
BACKGROUND Stingless bees or meliponines (family Apidae, subfamily Meliponinae, tribe Meliponini) are eusocial bees from tropical and subtropical regions. Propolis of Scaptotrigona aff. Postica (Latreille, 1807) is used in the state of Maranhão (Northeast Brazil) in ointments to treat tumors and wounds. Samples of propolis of Scaptotrigona aff. Postica (Apidae, Meliponini) were collected monthly from an apiary located in Barra do Corda (state of Maranhão, northeast Brazil). Extracts of the twelve samples were obtained with 80% ethanol. Constituents of the samples were characterized by HPLC-PAD-ESI-MS/MS analysis, amounting to 100 substances. RESULTS Representatives of several classes of secondary metabolites were characterized, including benzoic and cinnamic acids, flavonoids (chalcones, flavone-C-glycosides, flavonol aglycones and glycosides), alkyl and alkenyl resorcinols, xanthones, diterpenes, cycloartane-type triterpenoids, pentacyclic triterpenoids, pyrrolizidine alkaloids and hydroxycinnamic acid amides (HCAAs). Considerable qualitative differences in chemical composition among samples were observed, depending on the year period of collection. Principal Coordinate Analysis recognized three distinct year periods (Jan-Mar, April-Sep, Oct-Dec) according to the corresponding chemical profiles. CONCLUSION Comparing with previous studies, the present work indicates that considerable differences in chemical composition occur also from year to year. Contrary to most propolis types reported so far, which derives exclusively or mostly from a single botanical source, the propolis from Barra do Corda seemingly depends on several resin sources. It is suggested that chalcones and flavonols stem from Mimosa tenuiflora (Mimosoideae); resorcinols, xanthones and cycloartane-type triterpenoids, from fruits of Mangifera indica (Anacardiaceae); pyrrolizidine alkaloids, possibly from some Crotalaria species (Faboideae); HCAAs probably originate from pollen contaminating the propolis samples. The propolis of S. aff. Postica poses challenges and possibilities of study for apicultural researchers, chemists and pharmacologists.
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INTRODUCTION: Xanthones are metabolites with a variety of biological properties. The Clusiaceae family, which until recently included the genus Calophyllum, is recognised for its production of monohydroxylated and polyhydroxylated xanthones. Presently, C. brasiliense is the only Calophyllum spp. known to occur in the Yucatan peninsula. OBJECTIVE: To use a combination of traditional phytochemical methods and carbon-13 nuclear magnetic resonance (13 C-NMR) dereplication analysis to identify xanthones in the stem bark of C. brasiliense. MATERIAL AND METHODS: Initial fractionation and purification of the stem bark extract of C. brasiliense produced macluraxanthone (1). Additional xanthones, together with chromanones and terpenoids, were identified using 13 C-NMR dereplication analysis in different semipurified fractions obtained from the low and medium polarity fractions of the stem bark extract of C. brasiliense. RESULTS: Initial identification of macluraxanthone (1) was confirmed by 13 C-NMR dereplication analysis; additionally, 13 C-NMR dereplication analysis allowed the identification of a number of monohydroxylated and polyhydroxylated xanthones, together with chromanones and terpenoids. CONCLUSION: This study confirms C. brasiliense as a rich source of xanthones and the 13 C-NMR dereplication analysis as a suitable method to quickly identify the presence of different families of secondary metabolites in semipurified fractions.
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Calophyllum , Xantonas , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta , Extratos VegetaisRESUMO
This work reports the effect of hydroxy-xanthones (XAs) on 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers as determined by ultrasound velocimetry, densimetry and molecular dynamics simulations. XAs with different number of hydroxyl group were studied. Experimental results, in good agreement with molecular dynamics simulations, revealed that the presence of XAs in the systems studied increases fluidity while simultaneously decreses the compressibility of both membranes. This ´apparent contradiction´ ceases to exist when the particular geometrical structure of the xanthones is taken into account: the planar shape of their fused aromatic rings might allow them to pack efficiently among the hydrocarbon tails of the lipids, thus decreasing compressibility, while their presence weakens or disrupts methylene-methylene interchain interactions, thus increasing membrane fluidity and decreasing their melting temperature.
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Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Xantonas/química , Lipossomos/síntese química , Lipossomos/química , Fluidez de Membrana , Simulação de Dinâmica Molecular , Estrutura MolecularRESUMO
The chemical composition of Mangifera indica L. cv. "Kent" leaves was determined by HPLC-ESI-QTOF-MS/MS. Polyphenolic compounds characterized as benzophenone derivatives were the main components found in extracts (1, maclurin 3-C-(2-O-galloyl)-D- glucoside isomer; 2, maclurin 3-C-ï¢--D-glucoside; 3, iriflophenone 3-C-ï¢--D-glucoside; 5, maclurin 3-C-(2,3-di-O-galloyl)-ï¢--D-glucoside; 6, iriflophenone 3-C-(2-O-galloyl)-ï¢--D-glucoside; 7, methyl-iriflophenone 3-C-(2,6-di-O-galloyl)-ï¢--D-glucoside) and xanthones (4, mangiferin and 8, 6-O-galloyl-mangiferin). The estrogenic and antioxidant effects of aqueous extracts from Mangifera indica L. cv. "Kent" leaves on ovariectomized rats were determined by uterotrophic assay and malondialdehyde (MDA) levels in erythrocytes, bone, liver, and stomach. We conclude that the polyphenolic compounds from extracts act as exogenous antioxidant agents against oxidative damage in ovariectomized rats.
La composicioÌn quiÌmica de las hojas de Mangifera indica L. cv. "Kent" se determinoÌ por HPLC-ESI-QTOF-MS/MS. Compuestos polifenoÌlicos caracterizados como derivados de benzofenona fueron los componentes principales encontrados en los extractos (1, isoÌmero de la maclurina 3-C-(2-O-galoyil)-D-glucoÌsido; 2, maclurina 3-C-ß-D-glucoÌsido; 3, iriflofenona 3-C-ß-D-glucoÌsido; 5, maclurina 3-C-(2,3-di-O-galloiÌl)-ß-D-glucoÌsido; 6, iriflofenona 3-C-(2-O-galloil)-ß-D-glucoÌsido; 7, metil-iriflofenona 3-C-(2,6-di-O- galloyl)-ß-D-glucoÌsido) y xantonas (4, mangiferina y 8, 6-O-galoyil-mangiferina). Los efectos estrogeÌnicos y antioxidantes de los extractos acuosos de hojas de Mangifera indica L. cv. "Kent" en ratas ovariectomizadas se determinaron mediante ensayo uterotroÌfico y la medicioÌn de los niveles de malondialdehiÌdo (MDA) en eritrocitos, huesos, hiÌgado y estoÌmago. Concluimos que los compuestos polifenoÌlicos de los extractos actuÌan como agentes antioxidantes exoÌgenos contra el danÌo oxidativo en ratas ovariectomizadas.
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Animais , Feminino , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ovariectomia , Mangifera/química , Estrogênios/farmacologia , Antioxidantes/farmacologia , Estômago/efeitos dos fármacos , Benzofenonas/química , Osso e Ossos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Espécies Reativas de Oxigênio , Ratos Sprague-Dawley , Folhas de Planta/química , Espectrometria de Massas por Ionização por Electrospray , Etanol , Espectrometria de Massas em Tandem , Fígado/efeitos dos fármacos , Malondialdeído , Antioxidantes/químicaRESUMO
ABSTRACT A new xanthone: mangostanaxanthone VIIII [1,3,5,6,7-pentahydroxy-2-(3-methylbut-2-enyl)-8-(3-hydroxy-3-methylbut-1-enyl) xanthone] (5) and four known xanthones: mangostanaxanthones I (1) and II (2), γ-mangostin (3), and mangostanaxanthone VII (4) were separated and characterized from the acetone fraction of Garcinia mangostana L., Clusiaceae (mangosteen) pericarps. Their structures were established based on various spectroscopic analyses in addition to HRMS and comparison with the literature. The α-amylase inhibitory potential of the isolated metabolites was evaluated. Compounds 1, 2, and 5 had the highest activity with % inhibition 72.5, 86.5, and 81.8, respectively compared to acarbose (97.1%, reference α-amylase inhibitor). The molecular docking study of the tested metabolites was estimated to shade up the rational explanation of the α-amylase inhibitory activity results. Moreover, the pharmacokinetic parameters were assessed using Swiss ADME. It is noteworthy that 1, 2, and 5 had similar binding poses as the X-ray crystal structure of acarbose, whereas the other metabolites possessed different binding mode that decreased their inhibitory capacity. Thus, these data reinforced the health benefit of mangosteen as an alternative medicine to help lowering the postprandial glucose absorption. Therefore, it could have a good potential for the treatment of diabetes.
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ABSTRACT Species from the genus Mesua, Calophyllaceae, are rich source for phenolic compounds such as coumarin xanthone, and benzophenone derivatives. An investigation on the potential biologically active phenolic compounds 1-5 and crude extracts from the stem bark of Mesua hexapetala (Hook. f.) P.S. Ashton and Mesua beccariana (Baill.) Kosterm. for nitric oxide inhibitory activity on RAW 264.7 macrophage as well as anti-Bacillus activity on selected Bacillus were carried out. Hexapetarin (1), which we reported as a new compound isolated from M. hexapetala showed very good nitric oxide inhibitory activity with an IC50 value of 30.79 ± 2.68 µM. This compound also gave very significant activities towards Bacillus subtilis ATCC 6633, Bacillus cereus ATCC 33019, Bacillus megaterium ATCC 14581 and Bacillus pumilus ATCC 14884 in disc diffusion and minimum inhibitory concentrations assay. Moreover, 1,3,7-trihydroxy-2,4-di (3-methyl-2-butenyl)xanthone (2) isolated from M. hexapetala showed very significant nitric oxide inhibitory activity with an IC50 value of 12.41 ± 0.89 µM and does not exhibit anti-Bacillus activity on four types of Bacillus. Meanwhile, compounds 3-5 were inactive in the nitric oxide activity test and anti-Bacillus assay.
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The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.46-12.09µM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered asa potential lead compound towards new drugs for the treatment of Alzheimer's disease.
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Desenho de Fármacos , Xantonas/química , Xantonas/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Sítios de Ligação , Domínio Catalítico , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Ativação Enzimática/efeitos dos fármacos , Ligação de Hidrogênio , Simulação de Acoplamento MolecularRESUMO
Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000µM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC50 at 72h by MTT: 85.9µM) than on G0 phase-PBMCs (IC50 315.6µM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1µM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5µM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G0/G1 phase of the cell cycle (from 5µM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5µM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5µM) and frequency of hypodiploid cells (from 10µM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD50; 0.548g/kg. Approximately to 300µM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.
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Antineoplásicos Fitogênicos/farmacologia , Calophyllum/química , Dano ao DNA , Eritrócitos/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Extratos Vegetais/farmacologia , Xantonas/farmacologia , Adulto , Aneuploidia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Eritrócitos/patologia , Humanos , Concentração Inibidora 50 , Leucócitos Mononucleares/patologia , Masculino , Camundongos Endogâmicos BALB C , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Medição de Risco , Fatores de Tempo , Xantonas/isolamento & purificação , Xantonas/toxicidade , Adulto JovemRESUMO
Garcinia mangostana L. (Clusiaceae) is a tropical tree native to Southeast Asia known as mangosteen which fruits possess a distinctive and pleasant taste that has granted them the epithet of "queen of the fruits". The seeds and pericarps of the fruit have a long history of use in the traditional medicinal practices of the region, and beverages containing mangosteen pulp and pericarps are sold worldwide as nutritional supplements. The main phytochemicals present in the species are isoprenylated xanthones, a class of secondary metabolites with multiple reports of biological effects, such as antioxidant, pro-apoptotic, anti-proliferative, antinociceptive, anti-inflammatory, neuroprotective, hypoglycemic and anti-obesity. The diversity of actions displayed by mangosteen xanthones shows that these compounds target multiple signaling pathways involved in different pathologies, and place them as valuable sources for developing new drugs to treat chronic and degenerative diseases. This review article presents a comprehensive update of the toxicological findings on animal models, and the preclinical anticancer, analgesic, neuroprotective, antidiabetic and hypolipidemic effects of G. mangostana L. extracts and its main isolates. Pharmacokinetics, drug delivery systems and reports on dose-finding human trials are also examined.
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Garcinia mangostana/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Frutas/química , Humanos , Extratos Vegetais/química , Xantonas/química , Xantonas/farmacologiaRESUMO
ABSTRACT β-Glucuronidase inhibitors are suggested as potential hepatoprotective agents. Swertia chirayita (Roxb.) Buch.-Ham. ex C.B. Clarke, Gentianaceae, is known for its hepatoprotective and anti-hepatotoxic activity in Ayurvedic system of medicine for ages. This plant is substituted by other species like S. decussata Nimmo ex C.B. Clarke and S. bimaculata (Siebold & Zucc.) Hook. f. & Thomson ex C.B. Clarke. The aim of the study was to compare metabolite profile and β-glucuronidase inhibitory activity of these three important species of Swertia and to identify the active constituents. S. chirayita (IC50 210.97 µg/ml) and S. decussata (IC50 269.7 µg/ml) showed β-glucuronidase inhibitory activity significantly higher than that of silymarin, the known inhibitor of the enzyme. The activity of S. bimaculata was low. The metabolites present in the three species were analyzed by HPLC and GC-MS based metabolomics approach. Five amino acids, twenty one organic acids, one inorganic acid, eight fatty acids, twenty one phenols including xanthones, eight sugars, seven sugar alcohols, five terpenoids and amarogentin were identified. Activities of the xanthones mangiferin (IC50 16.06 µg/ml), swerchirin (IC50 162.84 µg/ml), decussatin (IC50 195.11 µg/ml), 1-hydroxy-3,5,8-trimethoxy xanthone (IC50 245.97 µg/ml), bellidifolin (IC50 390.26 µg/ml) were significantly higher than that of silymarin (IC50 794.62 µg/ml). Quinic acid (IC50 2.91 mg/ml), O-acetylsalicylic acid (IC50 48.4 mg/ml), citric acid (IC50 1.77 mg/ml), D-malic acid (IC50 14.82 mg/ml) and succinic acid (IC50 38.86 mg/ml) also inhibited the enzyme β-glucuronidase. The findings suggest that constituents, in addition to the xanthones, probably also contribute to the bioactivity of different Swertia species by synergistic effect. Further in vivo study is required to support the claim.
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The present study was designed to investigate the gastroprotective effect of xanthones 7-preniljacareubin (PJB), 1,3,5,6-tetrahydroxy xanthone (THX), 3-demethyl-2-geranyl-4-prenylbellidypholine (DGP) and 1,5,8-trihydroxy-4', 5'-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) isolated of branches from G. achachairu. Their structures were identified through the spectroscopic analysis in comparison with previously reported data. The xanthones were tested at dose of 10 mg/kg against ethanol 60%/HCl 0.3 N-induced gastric ulcer in female swiss mice. The xanthones PJB, THX, DGP and TDP exhibit gastroprotective effect after intraperitoneal treatment, but only the first two displayed anti-ulcer activity after oral administration. Both PJB and THX augmented the antioxidative capacity of tissue by an increase in glutathione levels, as well as were able to prevent an increase in myeloperoxidase activity and tumor necrosis factor level. On the other hand, only THX showed an in vitro free radical scavenger activity, and only PJB avoided mucus depletion on gastric mucosa, which was not associated with an increase in mucin production at glandular level. In addition, PJB and THX inhibited the in vitro H(+)K(+)-ATPase activity at similar range as omeprazole. Together, these results demonstrate the anti-ulcer efficacy of xanthones isolated from G. achachairu, which can contribute for future directions in the development of effective strategies to improve gastric diseases.
Assuntos
Garcinia/química , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Substâncias Protetoras/farmacologia , Xantonas/isolamento & purificação , Xantonas/farmacologia , Animais , Antiulcerosos/uso terapêutico , Antioxidantes/metabolismo , Compostos de Bifenilo/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Feminino , Sequestradores de Radicais Livres/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Glutationa/metabolismo , Imuno-Histoquímica , Inflamação/patologia , Camundongos , Mucinas/metabolismo , Peroxidase/metabolismo , Picratos/química , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Espectroscopia de Prótons por Ressonância Magnética , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Fator de Necrose Tumoral alfa/metabolismo , Xantonas/químicaRESUMO
Xanthones are secondary metabolites which have drawn considerable interest over the last decades due to their antimicrobial properties, among others. A great number of this kind of compounds has been therefore reported, but there is a limited amount of studies on screening for biological activity. Thus, as part of our research on antimicrobial agents of natural origin, a set of 272 xanthones were submitted to molecular docking (MD) calculations with a group of seven fungal and two viral enzymes. The results indicated that prenylated xanthones are important hits for inhibition of the analyzed enzymes. The MD scores were also analyzed by multivariate statistics. Important structural details were found to be crucial for the inhibition of the tested enzymes by the xanthones. In addition, the classification of active xanthones can be achieved by statistical analysis on molecular docking scores by an affinity-antifungal activity relationship approach. The obtained results therefore are a suitable starting point for the development of antifungal and antiviral agents based on xanthones.
Assuntos
Antifúngicos/química , Antivirais/química , Proteínas Fúngicas/química , Simulação de Acoplamento Molecular , Proteínas Virais/química , Xantonas/química , Relação Estrutura-AtividadeRESUMO
Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α-mangostin and a new compound, δ-mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α-Mangostin was more active against the resistant Plasmodium falciparum chloroquine-resistant (FCR3) strain (IC50 = 0.2 ± 0.01 µM) than δ-mangostin (IC50 = 121.2 ± 1.0 µM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances.
Assuntos
Antimaláricos/farmacologia , Garcinia mangostana/química , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Xantonas/farmacologia , Animais , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Hemólise , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia/tratamento farmacológico , Células U937RESUMO
OBJECTIVE: To evaluate the Tabernaemontana catharinensis ethyl acetate fraction hypoglycemic and antioxidant activity through the peripheral glycemic dosage and enzymatic tests. Methods: Male rats were divided into 6 groups: control, diabetic control, control extract 50, diabetic extract 50, control extract 80, diabetic extract 80. In diabetic group animals alloxan (150mg/Kg) was administered to induce Diabetes Mellitus. The animals were beheaded following 15 days of treatment with extract or distilled water and the blood was collected in order to perform oxidative stress tests. Results: The diabetic control group showed high levels of glucose, increased levels of thiobarbituric acid and superoxide dismutase activity, and decreased activity of catalase and glutathione peroxidase enzymes. The diabetic animals that received 50mg/Kg and 80mg/Kg of extract showed a decrease in thiobarbituric acid levels and an increase of glutathione peroxidase activity when compared to the diabetic control group. It was observed that only animals treated with 80mg/Kg of extract had positive results regarding superoxide dismutase. Conclusions: The Tabernaemontana catharinensis ethyl acetate fraction when orally administered for 14 consecutive days at doses of 50mg/Kg and 80mg/Kg reduces the oxidative stress induced by alloxan administration
OBJETIVO: Avaliar a ação hipoglicemiante e antioxidante da fração acetato de etila do extrato de Tabernaemontana catharinensis através da dosagem glicêmica periférica e testes enzimáticos. MÉTODOS: Ratos machos foram divididos em seis grupos: controle, controle diabético, controle extrato 50, diabético extrato 50, controle extrato 80, diabético extrato 80. Nos animais dos grupos diabéticos foi induzida Diabetes Mellitus pela administração de 150mg/Kg de aloxana. Após 15 dias de tratamento com a fração acetato de etila de Tabernaemontana catharinensis ou água destilada, os animais foram decapitados e o sangue foi coletado para realização dos testes de estresse oxidativo. RESULTADOS: O grupo controle diabético apresentou níveis elevados de glicose, aumento dos níveis de ácido tiobarbitúrico e atividade da superóxido dismutase, e diminuição da atividade das enzimas catalase e glutationa peroxidase. Os animais dos grupos diabéticos tratados com 50 e 80mg/Kg do extrato apresentaram redução nos níveis de ácido tiobarbitúrico e aumento da atividade de glutationa peroxidase quando comparado ao grupo controle diabético. Apenas os animais que receberam o extrato na dose de 80mg/Kg obtiveram resultados positivos em relação ao superóxido dismutase. CONCLUSÕES: A fração acetato de etila de Tabernaemontana catharinensis, quando administrada por 14 dias consecutivos, via oral, nas doses de 50 e 80mg/Kg, promove redução nos níveis de estresse oxidativo gerado pela administração de aloxana