Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 502
Filtrar
1.
J Chem Ecol ; 45(11-12): 926-933, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31758292

RESUMO

Chemical examination of plant constituents responsible for oviposition by a Magnoliaceae-feeding butterfly, Graphium doson, was conducted using its major host plant, Michelia compressa. A methanol extract prepared from young leaves of the plant elicited a strong oviposition response from females. The methanolic extract was then separated by solvent partition into three fractions: CHCl3, i-BuOH, and aqueous fractions. Active substance(s) resided in both i-BuOH- and water-soluble fractions. Bioassay-guided further fractionation of the water-soluble substances by means of various chromatographic techniques led to the isolation of an oviposition stimulant. The stimulant was identified as D-(+)-pinitol on the basis of 13C NMR spectra and physicochemical properties. D-(+)-Pinitol singly exhibited a moderate oviposition-stimulatory activity at a dose of 150 µg/cm2. This compound was present also in another host plant, Magnolia grandiflora, in a sufficient amount to induce oviposition behavior of G. doson females. Certain cyclitols including D-(+)-pinitol have been reported to be involved in stimulation of oviposition by some Aristolochiaceae- and Rutaceae-feeding papilionid butterflies. A possible pathway of phytochemical-mediated host shifts in the Papilionidae, in which certain cyclitols could enact important mediators, is discussed in relation to the evolution of cyclitol biosynthesis in plants.


Assuntos
Magnolia/química , Oviposição/efeitos dos fármacos , Extratos Vegetais/química , Animais , Butanóis/química , Borboletas , Ciclitóis/química , Ciclitóis/metabolismo , Feminino , Especificidade de Hospedeiro , Interações Hospedeiro-Parasita , Inositol/análogos & derivados , Inositol/química , Inositol/metabolismo , Magnolia/metabolismo , Extratos Vegetais/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Solubilidade , Água/química
2.
J Biochem ; 166(5): 441-448, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504617

RESUMO

Glycosylinositol phosphoceramide (GIPC) is the most abundant sphingolipid in plants and fungi. Recently, we detected GIPC-specific phospholipase D (GIPC-PLD) activity in plants. Here, we found that GIPC-PLD activity in young cabbage leaves catalyzes transphosphatidylation. The available alcohol for this reaction is a primary alcohol with a chain length below C4. Neither secondary alcohol, tertiary alcohol, choline, serine nor glycerol serves as an acceptor for transphosphatidylation of GIPC-PLD. We also found that cabbage GIPC-PLD prefers GIPC containing two sugars. Neither inositol phosphoceramide, mannosylinositol phosphoceramide nor GIPC with three sugar chains served as substrate. GIPC-PLD will become a useful catalyst for modification of polar head group of sphingophospholipid.


Assuntos
Biocatálise , Brassica/enzimologia , Ceramidas/metabolismo , Inositol/metabolismo , Fosfatidilcolinas/metabolismo , Fosfolipase D/metabolismo , Folhas de Planta/enzimologia , Brassica/química , Ceramidas/química , Inositol/análogos & derivados , Inositol/química , Estrutura Molecular , Fosfatidilcolinas/química , Fosfolipase D/química , Folhas de Planta/química
3.
ACS Chem Biol ; 14(8): 1717-1726, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31305987

RESUMO

Detergents are widely used to isolate membrane proteins from lipid bilayers, but many proteins solubilized in conventional detergents are structurally unstable. Thus, there is major interest in the development of novel amphiphiles to facilitate membrane protein research. In this study, we have designed and synthesized novel amphiphiles with a rigid scyllo-inositol core, designated scyllo-inositol glycosides (SIGs). Varying the headgroup structure allowed the preparation of three sets of SIGs that were evaluated for their effects on membrane protein stability. When tested with a few model membrane proteins, representative SIGs conferred enhanced stability to the membrane proteins compared to a gold standard conventional detergent (DDM). Of the novel amphiphiles, a SIG designated STM-12 was most effective at preserving the stability of the multiple membrane proteins tested here. In addition, a comparative study of the three sets suggests that several factors, including micelle size and alkyl chain length, need to be considered in the development of novel detergents for membrane protein research. Thus, this study not only describes new detergent tools that are potentially useful for membrane protein structural study but also introduces plausible correlations between the chemical properties of detergents and membrane protein stabilization efficacy.


Assuntos
Proteínas de Bactérias/metabolismo , Detergentes/química , Glicosídeos/química , Inositol/análogos & derivados , Inositol/química , Proteínas de Membrana/metabolismo , Bactérias/química , Detergentes/síntese química , Glicosídeos/síntese química , Conformação Molecular , Estabilidade Proteica , Rhodobacter capsulatus/química , Salmonella typhimurium/enzimologia
4.
Chem Pharm Bull (Tokyo) ; 67(6): 540-545, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155559

RESUMO

Fixed-dose combination (FDC) medicines containing two or more active pharmaceutical ingredients (APIs) in a single dosage form have been reported to improve patient adherence to a greater extent than single dosages of individual components (ICs). Orally disintegrating tablets (ODTs) are easier to swallow than conventional tablets. The aim of this study was to elucidate the clinical pharmaceutical characteristics of taking a FDC-ODT and two IC-ODTs. We prepared three ODTs containing mitiglinide, voglibose, and mitiglinide/voglibose and three corresponding placebo ODTs and performed 2 independent clinical trials with 13 healthy subjects (mean age, 23.4 ± 1.6 years). One trial evaluated the ease of taking tablets and the amount of water required for taking the tablets; placebo ODTs were used in order to avoid administering APIs. The other trial evaluated the bitterness, sweetness and overall palatability of ODTs containing APIs during disintegration and after spitting out. Ease and taste were evaluated using both a visual analog scale (VAS) and a verbal rating scale (VRS). The results of the VAS and VRS evaluation indicated that FDC-ODT could ease tablet intake unlike IC-ODTs. In addition, FDC-ODT reduced the amount of water required for tablet intake in contrast to IC-ODTs. Taste evaluation results did not reveal any difference between FDC-ODT and IC-ODTs, except for the sweetness score after spitting out. In conclusion, FDC-ODT is easy to take and can help improve patient adherence.


Assuntos
Inositol/análogos & derivados , Isoindóis/química , Comprimidos/administração & dosagem , Administração Oral , Adulto , Composição de Medicamentos , Feminino , Humanos , Inositol/química , Masculino , Efeito Placebo , Solubilidade , Paladar/fisiologia , Água/administração & dosagem , Adulto Jovem
5.
Molecules ; 24(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970539

RESUMO

Thermal energy storage systems work in conjunction with solar technologies with the aim of increasing their dispatchability and competitiveness in the energy market. Among others, latent heat thermal energy storage systems have become an appealing research subject and many efforts have therefore been invested in selecting the best phase change material (PCM) to fit the final application. In this study, an extended corrosion characterization was performed for two PCM candidates, solar salt (40 wt.% KNO3/60 wt.% NaNO3) and myo-inositol (C6H12O6), to be applied in Fresnel solar plants. Corrosion rates were determined in aluminium, stainless steel (AISI 304), carbon steel (AISI 1090), and copper by gravimetric tests, gauging the weight loss after 2000 h of immersion at 250 °C. The corrosion products were characterized by scanning electron microscopy (SEM) and x-ray diffraction (XRD). The corrosion tests carried out with myo-inositol did not show accurate enough results to draw conclusions regarding corrosion on the metals. However, it was observed that this sugar alcohol strongly sticks to the metal specimens, making myo-inositol extremely difficult to manage as an energy storage material. Therefore, the present paper discourages the use of myo-inositol as a PCM beyond its corrosion rate.


Assuntos
Inositol/química , Aço Inoxidável/química , Álcoois Açúcares/química , Corrosão , Energia Solar
6.
Chem Res Toxicol ; 32(2): 265-284, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30604967

RESUMO

Previously, we demonstrated that treatment of rats with myo-inositol plus ethanolamine (ME) elevated brain ethanolamine plasmalogens (PE-Pls) and protected against phosphine-induced oxidative stress. Here we tested the hypothesis that ME treatment elevates PE-Pls in a neuro-2A (N2A) cell culture system and protects against hydrogen peroxide (H2O2)-induced oxidative stress, and we assessed the effects of treatments using myo-inositol with or without (+/-) ethanolamine on ethanolamine phospholipids (PLs) and cell viability following H2O2 exposure. Cells were treated with equimolar amounts (500 µM) of myo-inositol, ethanolamine (Etn), or their combination (ME) for 24 h, followed by an additional 24 h exposure to 650 µM H2O2. NMR analyses evaluated the treatment effects on Etn PLs, while LC-MS/MS analyses assessed the molecular species of Etn PLs preferentially affected by ME and H2O2 treatments, especially PE-Pls and their degradation byproducts-lysophosphatidylethanolamine (LPE) and glycerophosphoethanolamine (GPE). Only ME influenced the cellular levels of PLs. ME yielded a 3-fold increase in PE-Pls and phosphatidylethanolamine (PE) ( p < 0.001) and a preferential 60% increase in PE-Pls containing saturated and monounsaturated fatty acids (SFA+MUFA), while polyunsaturated fatty acid (PUFA) species increased by only 10%. Exposing cells to 650 µM H2O2 caused a significant cell death (56% viability), a 27% decrease in PE-Pls, a 201% increase in PUFA-rich LPE, and a ca. 3-fold increase in GPE. H2O2 had no impact on PE, suggesting that LPE and GPE were primarily the byproducts of PE-Pls (not PE) degradation. Surprisingly, ME pretreatment ameliorated H2O2 effects and significantly increased cell survival to 80% ( p < 0.05). Cellular PE-Pls levels prior to H2O2 treatment were highly correlated ( R2 = 0.95) with cell survival, suggesting a relationship between PE-Pls and cell protection. Data suggest that a preferential increase in PE-Pls containing SFA+MUFA species may protect cells from oxidative stress. Such studies aid in our understanding of the neuroprotective mechanisms that may be associated with plasmalogens and the relevance of these phospholipids to neurodegenerative diseases/disorders.


Assuntos
Etanolamina/farmacologia , Inositol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Plasmalogênios/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Etanolamina/química , Peróxido de Hidrogênio/toxicidade , Inositol/química , Camundongos , Plasmalogênios/análise , Espectrometria de Massas em Tandem
7.
Chembiochem ; 20(2): 172-180, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30098105

RESUMO

Phosphatidylinositol (PI) lipids control critical biological processes, so aberrant biosynthesis often leads to disease. As a result, the capability to track the production and localization of these compounds in cells is vital for elucidating their complex roles. Herein, we report the design, synthesis, and application of clickable myo-inositol probe 1 a for bioorthogonal labeling of PI products. To validate this platform, we initially conducted PI synthase assays to show that 1 a inhibits PI production in vitro. Fluorescence microscopy experiments next showed probe-dependent imaging in T-24 human bladder cancer and Candida albicans cells. Growth studies in the latter showed that replacement of myo-inositol with probe 1 a led to an enhancement in cell growth. Finally, fluorescence-based TLC analysis and mass spectrometry experiments support the labeling of PI lipids. This approach provides a promising means for tracking the complex biosynthesis and trafficking of these lipids in cells.


Assuntos
Corantes Fluorescentes/química , Inositol/química , Engenharia Metabólica , Fosfatidilinositóis/química , Candida albicans/citologia , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Células Cultivadas , Química Click , Corantes Fluorescentes/síntese química , Humanos , Inositol/síntese química , Imagem Óptica
8.
Redox Biol ; 20: 130-145, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30308476

RESUMO

Low molecular weight (LMW) thiols play an important role as thiol-cofactors for many enzymes and are crucial to maintain the reduced state of the cytoplasm. Most Gram-negative bacteria utilize glutathione (GSH) as major LMW thiol. However, in Gram-positive Actinomycetes and Firmicutes alternative LMW thiols, such as mycothiol (MSH) and bacillithiol (BSH) play related roles as GSH surrogates, respectively. Under conditions of hypochlorite stress, MSH and BSH are known to form mixed disulfides with protein thiols, termed as S-mycothiolation or S-bacillithiolation that function in thiol-protection and redox regulation. Protein S-thiolations are widespread redox-modifications discovered in different Gram-positive bacteria, such as Bacillus and Staphylococcus species, Mycobacterium smegmatis, Corynebacterium glutamicum and Corynebacterium diphtheriae. S-thiolated proteins are mainly involved in cellular metabolism, protein translation, redox regulation and antioxidant functions with some conserved targets across bacteria. The reduction of protein S-mycothiolations and S-bacillithiolations requires glutaredoxin-related mycoredoxin and bacilliredoxin pathways to regenerate protein functions. In this review, we present an overview of the functions of mycothiol and bacillithiol and their physiological roles in protein S-bacillithiolations and S-mycothiolations in Gram-positive bacteria. Significant progress has been made to characterize the role of protein S-thiolation in redox-regulation and thiol protection of main metabolic and antioxidant enzymes. However, the physiological roles of the pathways for regeneration are only beginning to emerge as well as their interactions with other cellular redox systems. Future studies should be also directed to explore the roles of protein S-thiolations and their redox pathways in pathogenic bacteria under infection conditions to discover new drug targets and treatment options against multiple antibiotic resistant bacteria.


Assuntos
Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/metabolismo , Oxirredução , Processamento de Proteína Pós-Traducional , Animais , Cisteína/análogos & derivados , Cisteína/biossíntese , Cisteína/química , Cisteína/farmacologia , Glucosamina/análogos & derivados , Glucosamina/biossíntese , Glucosamina/química , Glucosamina/farmacologia , Glicopeptídeos/biossíntese , Glicopeptídeos/química , Glicopeptídeos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Inositol/biossíntese , Inositol/química , Inositol/farmacologia , Modelos Biológicos , Oxirredução/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Relação Estrutura-Atividade , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo
9.
Crit Rev Food Sci Nutr ; 59(7): 1124-1136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29053004

RESUMO

A growing body of research has investigated the association between inositol and diabetes. The purpose of this review is to report through a systematic way the current scientific evidence relating potential benefits of inositol isomers on diabetes/gestational diabetes. The screening of the studies published last decade was performed in 4 databases (Pubmed-Web of Science-The Cochrane Library-Lilacs). Among the 1640 studies identified in the search, only 26 studies had sufficient data to be included in the systematic review. The available literature suggests that inositol seems to be provide improvements in fasting blood glucose and other biochemical results, which are among the most important parameters in diabetic individuals. Although there are some studies demonstrating that inositol may be effective in prevention and treatment of diabetes/gestational diabetes, conduction of studies with larger sample and longer follow-up duration is required for it to be represented as an effective strategy in management of diabetes.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/prevenção & controle , Inositol/química , Inositol/uso terapêutico , Animais , Glicemia/metabolismo , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Jejum , Feminino , Humanos , Gravidez
10.
J Biosci Bioeng ; 127(5): 549-553, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30503170

RESUMO

Two new nanaomycin analogs, nanaomycin I and J, were isolated from a cultured broth of an actinomycete strain, "Streptomyces rosa subsp. notoensis" OS-3966. In our previous study, we have confirmed the occurrence of nanaomycin I (m/z = 482 [M + H]+) that lacks a pseudo-disaccharide from the mycothiol of nanaomycin H under same culture condition. In this study, to confirm the structure of nanaomycin I, the strain "S. rosa subsp. notoensis" OS-3966 was re-cultured and the target compound with m/z = 482 [M + H]+ was isolated. Furthermore, we discovered another new analog, designated as nanaomycin J in isolating nanaomycin I. The NMR analyses revealed that the structures of nanaomycin I and J are N-acetylcysteine S-conjugates without a pseudo-disaccharide and N-acetylcysteine S-conjugates without a myo-inositol of nanaomycin H, respectively. The relative configurations of the tetrahydropyrane moiety of nanaomycin I and J were determined by rotating-frame overhauser effect spectroscopy (ROESY) analysis. Absolute configurations of the N-acetylcysteine moiety of nanaomycin I and J were determined by advanced Marfey's analyses for acid hydrolysis of de-sulfurized nanaomycin I and J with Raney nickel. Nanaomycin I and J showed moderate cytotoxicity against several human tumor cell lines.


Assuntos
Anti-Infecciosos/metabolismo , Cisteína/metabolismo , Glicopeptídeos/metabolismo , Inositol/metabolismo , Streptomyces/metabolismo , Anti-Infecciosos/química , Sobrevivência Celular/efeitos dos fármacos , Cisteína/química , Glicopeptídeos/química , Humanos , Inositol/química , Estrutura Molecular , Streptomyces/química
11.
Molecules ; 23(12)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513982

RESUMO

Osmolytes are small organic compounds that can affect the stability of proteins in living cells. The mechanism of osmolytes' protective effects on protein structure and dynamics has not been fully explained, but in general, two possibilities have been suggested and examined: a direct interaction of osmolytes with proteins (water replacement hypothesis), and an indirect interaction (vitrification hypothesis). Here, to investigate these two possible mechanisms, we studied myoglobin-osmolyte systems using FTIR, UV-vis, CD, and femtosecond IR pump-probe spectroscopy. Interestingly, noticeable changes are observed in both the lifetime of the CO stretch of CO-bound myoglobin and the spectra of UV-vis, CD, and FTIR upon addition of the osmolytes. In addition, the temperature-dependent CD studies reveal that the protein's thermal stability depends on molecular structure, hydrogen-bonding ability, and size of osmolytes. We anticipate that the present experimental results provide important clues about the complicated and intricate mechanism of osmolyte effects on protein structure and dynamics in a crowded cellular environment.


Assuntos
Mioglobina/química , Osmose , Betaína/química , Dicroísmo Circular , Inositol/química , Mioglobina/metabolismo , Estabilidade Proteica , Sorbitol/química , Espectrofotometria Infravermelho/métodos , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Taurina/química , Temperatura Ambiente , Trealose/química
12.
Molecules ; 23(12)2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30486330

RESUMO

Osteoporosis is widely recognized as a major health problem caused by an inappropriate rate of bone resorption compared to bone formation. Previously we showed that d-pinitol inhibits osteoclastogenesis but has no effect on osteoblastogenesis. However, the effect on osteoblast differentiation of its isomer, l-quebrachitol, has not yet been reported. The purpose of this study was, therefore, to investigate whether l-quebrachitol promotes the osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. Moreover, the molecular mechanism of action of l-quebrachitol was further explored. Here, it is shown for the first time that l-quebrachitol significantly promotes proliferation and cell DNA synthesis. It also enhances mineralization accompanied by increases in mRNA expression of bone matrix proteins including alkaline phosphatase (ALP), collagen type I (ColI), osteocalcin (OCN), and osteopontin (OPN). In addition, l-quebrachitol upregulates the mRNA and protein expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2), while down-regulating the receptor activator of the nuclear factor-κB ligand (RANKL) mRNA level. Moreover, the expression of regulatory genes associated with the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/ß-catenin signaling pathways are also upregulated. These findings indicate that l-quebrachitol may promote osteoblastogenesis by triggering the BMP-2-response as well as the Runx2, MAPK, and Wnt/ß-catenin signaling pathway.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Inositol/análogos & derivados , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , DNA/biossíntese , Inositol/química , Inositol/isolamento & purificação , Inositol/farmacologia , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Borracha/química , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
13.
Biochem Biophys Res Commun ; 504(1): 315-320, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30180952

RESUMO

D-ononitol epimerase (OEP) catalyzes the conversion of D-ononitol to D-pinitol, which is the last step in the biosynthetic pathway, where myo-inositol is converted to pinitol in higher plants. In this study, OEP cDNA was isolated from Glycine max (GmOEP) and was functionally characterized, which confirmed that GmOEP expression was induced by high salinity and drought stress treatments. To understand the biological function of GmOEP, transgenic Arabidopsis plants overexpressing this protein were constructed. The transgenic Arabidopsis plants displayed enhanced tolerance to high salinity and drought stress treatments.


Assuntos
Arabidopsis/genética , Arabidopsis/metabolismo , Inositol/análogos & derivados , Sais/química , Proteínas de Arabidopsis/metabolismo , Secas , Etiquetas de Sequências Expressas , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Inositol/biossíntese , Inositol/química , Plantas Geneticamente Modificadas/metabolismo , Tolerância ao Sal/genética , Plântula/metabolismo , Cloreto de Sódio/química , Soja/metabolismo , Estresse Fisiológico
14.
Biomaterials ; 184: 20-30, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195802

RESUMO

Successful immunogene therapy depends not only on the therapeutic gene but also on the gene delivery vector. In this study, we synthesized a novel copolymer consisting of low-molecular-weight polyethylenimine (PEI) cross-linked by myo-inositol (INO) and conjugated with a galactose-grafted PEG chain, named LA-PegPI. We characterized the chemical structure and molecular weight of the copolymer and particle properties of LA-PegPI/pDNA. Furthermore, we showed that LA-PegPI/pDNA polyplexes possessed excellent stability in physiological salt solution, low cytotoxicity, and high transfection efficiency in the asialoglycoprotein receptor (ASGPR)-positive liver cells in vitro. Importantly, we also showed that through intraperitoneal injection of LA-PegPI/pDNA nanoparticles, the reporter gene was forcefully expressed in the liver hepatocytes of mice. Finally, we documented that intraperitoneal injection of LA-PegPI/pIL15 nanoparticles effectively suppressed tumor growth and prolonged survival time of tumor-bearing mice via activation of CD8+ T cells and NK cells and upregulation of the cytokines IFN-γ, TNF, and IL12 in an orthotopic hepatocellular carcinoma mouse model. Interestingly, LA-PegPI/pluc nanoparticles could effectively stimulate the proliferation of NK cells and inhibit tumor growth in this model. In summary, LA-PegPI is a useful gene vector for immunogene therapy of hepatocellular carcinoma, and its potential for clinical application warrants further study.


Assuntos
Receptor de Asialoglicoproteína/genética , Carcinoma Hepatocelular/terapia , Galactose/química , Interleucina-15/metabolismo , Neoplasias Hepáticas/terapia , Polietilenoglicóis/química , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Reagentes para Ligações Cruzadas/química , DNA/administração & dosagem , Portadores de Fármacos , Feminino , Genes Reporter , Hepatócitos/patologia , Humanos , Imunoterapia , Inositol/química , Interleucina-15/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Camundongos Endogâmicos BALB C , Peso Molecular , Nanopartículas/química , Plasmídeos , Polietilenoimina/química
15.
Bioorg Med Chem Lett ; 28(14): 2555-2560, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29866516

RESUMO

Stereoselective and efficient synthesis of hydroxymethyl-substituted rac-quercitols (13-15) was achieved, starting from cis-furan (Kobayashi, 2008) with photooxygenation reaction, which is readily available by the reduction of cis-phtalic anhydride. α- and ß-Glucosidase enzyme activity of the target molecules was evaluated and good inhibitor activity was seen. One- and two-dimensional NMR spectroscopy, IR spectroscopy and X-ray crystallography were utilized in the structure characterization of products.


Assuntos
Glucosidases/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Inositol/análogos & derivados , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Inositol/síntese química , Inositol/química , Inositol/farmacologia , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade
16.
Curr Drug Deliv ; 15(9): 1305-1311, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29745333

RESUMO

BACKGROUND: Myo-inositol is a natural molecule with important therapeutic applications and an impaired oral absorption may result in a reduced clinical effect. Aim of this study was to determine if the combined oral administration of α-lactalbumin and myo-inositol in healthy subjects, could increase the plasma level of myo-inositol administered alone. In vitro studies on human differentiated intestinal Caco-2 cells were also conducted to identify the mechanisms involved in myo-inositol absorption. OBJECTIVE: The in vivo study was conducted on healthy volunteers in two phases. Subjects received a single oral myo-inositol dose. After 7 days washout, the same subjects were administered a single dose of myo-inositol and α-lactalbumin. Cmax, Tmax and AUC for myo-inositol in plasma were calculated from samples collected at different times. Transepithelial myo-inositol passage, with or without addition of digested α-lactalbumin, was measured in vitro in differentiated Caco-2 cells and compared to transepithelial electrical resistance and phenol red passage. RESULTS: The bioavailability of myo-inositol was modified by the concomitant administration of α- lactalbumin. Although peak concentration of myo-inositol at 180 min (Tmax) was similar for both treatments, administration of α-lactalbumin with myo-inositol in a single dose, significantly increased the plasma concentrations of myo-inositol compared to when administered alone. In vitro, myo-inositol absorption in Caco-2 cells was improved in the presence of digested α-lactalbumin, and this change was associated with an increase in tight junction permeability. CONCLUSION: Better myo-inositol absorption when orally administered with α-lactalbumin can be beneficial in non-responder patients. Preliminary in vitro findings suggest that peptides deriving from α- lactalbumin digestion may modulate tight junction permeability allowing increased absorption of myoinositol.


Assuntos
Inositol/química , Intestinos/química , Lactalbumina/química , Administração Oral , Adolescente , Adulto , Células CACO-2 , Feminino , Voluntários Saudáveis , Humanos , Inositol/administração & dosagem , Inositol/metabolismo , Absorção Intestinal , Lactalbumina/administração & dosagem , Lactalbumina/metabolismo , Masculino , Adulto Jovem
17.
Carbohydr Res ; 463: 32-36, 2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-29751207

RESUMO

scyllo-Inositol derived 1,2-trans-diequatorial halohydrins can be efficiently converted to the corresponding epoxides in the presence of lithium hydride. The structure of one of the epoxides was determined by single crystal X-ray diffraction analysis. This provides a potential route for the preparation of ring modified inositol derivatives. DFT calculations suggest that this epoxide formation could be proceeding through the intermediacy of the cyclohexane ring-inverted axial-rich conformer (1,2-trans-diaxial halohydrin). This is supported by the results of DFT calculations on the formation of inositol orthoformate, where the product is locked in the axial-rich conformation, while the starting inositol has the equatorial-rich conformation.


Assuntos
Compostos de Epóxi/síntese química , Inositol/química , Lítio/química , Compostos de Epóxi/química , Indicadores e Reagentes , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Difração de Raios X
18.
J Agric Food Chem ; 66(23): 5741-5745, 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29793339

RESUMO

Quercitol is a cyclohexanepentol that has been recognized as a biomarker of plants in genus Quercus, which includes oak. As a result of its glucose-like structure, it has been introduced as an alternative chiral building block in the synthesis of several bioactive compounds. Our continuing investigations on the synthesis of antidiabetic agents from quercitol have demonstrated that this chiral synthon can generate diverse structural features with improved hypoglycemic activity.


Assuntos
Hipoglicemiantes/síntese química , Inositol/análogos & derivados , Quercus/química , Animais , Biomarcadores/análise , Biomarcadores/química , Inositol/análise , Inositol/química , Conformação Molecular , Estrutura Molecular , Ratos , Estereoisomerismo , alfa-Glucosidases/metabolismo
19.
Acta Diabetol ; 55(8): 805-812, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29774465

RESUMO

AIMS: Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. The aim of the study is to compare the effect of different dosages of inositol stereoisomers supplementation on insulin resistance levels and several maternal-fetal outcomes in GDM women. METHODS: Participants were randomly allocated to receive daily: 400 mcg folic acid (control treatment), 4000 mg myo-inositol plus 400 mcg folic acid (MI treatment), 500 mg D-chiro-inositol plus 400 mcg folic acid (DCI treatment) or 1100/27.6 mg myo/D-chiro-inositol plus 400 mcg folic acid (MI plus DCI treatment). The homeostasis model assessment of insulin resistance (HOMA-IR) was measured at the diagnosis of GDM and after 8 weeks of treatment. Secondary outcomes, obstetric outcomes and any maternal or fetal complication at delivery were also collected. RESULTS: Eighty GDM women were assigned to one of the four arms of study (20 per arm). A significant delta decrease in HOMA-IR index was found in subjects of MI group without insulin therapy compared to control group (p < 0.001). A lower variation in average weight gain (at delivery vs pre-pregnancy and OGTT period) was detected in MI group vs control group (p = 0.001 and p = 0.019, respectively). Moreover, women exposed to MI and MI plus DCI required a significantly lower necessity of an intensified insulin treatment. Women of the control group had newborns with higher birth weight compared with women treated with inositol (p = 0.032). CONCLUSIONS: Our study provides interesting but preliminary results about the potential role of inositol stereoisomers supplementation in the treatment of GDM on insulin resistance levels and several maternal-fetal outcomes. Further studies are required to examine the optimal and effective dosages of different inositol supplements. CLINICAL TRIAL REG. NO.: NCT02097069, ClinicalTrial.gov.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Inositol/administração & dosagem , Adolescente , Adulto , Diabetes Gestacional/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Inositol/química , Resistência à Insulina , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Estereoisomerismo , Adulto Jovem
20.
Appl Microbiol Biotechnol ; 102(11): 4641-4651, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29663050

RESUMO

(-)-vibo-Quercitol is a deoxyinositol (1L-1,2,4/3,5-cyclohexanepentol) that occurs naturally in low concentrations in oak species, honeydew honey, and Gymnema sylvestre. The author's research group recently reported that (-)-vibo-quercitol and scyllo-quercitol (2-deoxy-myo-inositol, 1,3,5/2,4-cyclohexanepentol), a stereoisomer of (-)-vibo-quercitol, are stereoselectively synthesized from 2-deoxy-scyllo-inosose by the reductive reaction of a novel (-)-vibo-quercitol 1-dehydrogenase in Burkholderia terrae and of a known scyllo-inositol dehydrogenase in Bacillus subtilis, respectively. The author's research group therefore identified two enzymes capable of producing both stereoisomers of deoxyinositols, which are rare in nature. (-)-vibo-Quercitol and scyllo-quercitol are potential intermediates for pharmaceuticals. In this review, the author describes the biosynthesis and enzymatic production of quercitols and myo-inositol stereoisomers and their application in the production of potential pharmaceuticals.


Assuntos
Bacillus subtilis/enzimologia , Burkholderiaceae/enzimologia , Indústria Farmacêutica/métodos , Inositol/biossíntese , Preparações Farmacêuticas/síntese química , Inositol/química , Inositol/metabolismo , Oxirredutases/isolamento & purificação , Oxirredutases/metabolismo , Estereoisomerismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA