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1.
J Microbiol Biotechnol ; 34(6): 1356-1364, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38754998

RESUMEN

Isoamyl fatty acid esters (IAFEs) are widely used as fruity flavor compounds in the food industry. In this study, various IAFEs were synthesized from isoamyl alcohol and various fatty acids using a cutinase enzyme (Rcut) derived from Rhodococcus bacteria. Rcut was immobilized on methacrylate divinylbenzene beads and used to synthesize isoamyl acetate, butyrate, hexanoate, octanoate, and decanoate. Among them, Rcut synthesized isoamyl butyrate (IAB) most efficiently. Docking model studies showed that butyric acid was the most suitable substrate in terms of binding energy and distance from the active site serine (Ser114) γ-oxygen. Up to 250 mM of IAB was synthesized by adjusting reaction conditions such as substrate concentration, reaction temperature, and reaction time. When the enzyme reaction was performed by reusing the immobilized enzyme, the enzyme activity was maintained at least six times. These results demonstrate that the immobilized Rcut enzyme can be used in the food industry to synthesize a variety of fruity flavor compounds, including IAB.


Asunto(s)
Hidrolasas de Éster Carboxílico , Enzimas Inmovilizadas , Aromatizantes , Simulación del Acoplamiento Molecular , Rhodococcus , Enzimas Inmovilizadas/metabolismo , Enzimas Inmovilizadas/química , Rhodococcus/enzimología , Rhodococcus/metabolismo , Aromatizantes/metabolismo , Aromatizantes/química , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/química , Ésteres/metabolismo , Ésteres/química , Pentanoles/metabolismo , Pentanoles/química , Ácidos Grasos/metabolismo , Ácidos Grasos/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Temperatura , Especificidad por Sustrato , Ácido Butírico/metabolismo , Ácido Butírico/química , Dominio Catalítico
2.
Biotechnol Bioeng ; 119(2): 550-565, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34821376

RESUMEN

Environmental growth-inhibition conditions (GICs) have been used extensively for increasing cell-specific productivity (qP ) of Chinese hamster ovary (CHO) cells, with the most common being temperature downshift and sodium butyrate (NaBu) treatment. B lymphocyte-induced maturation protein-1 (BLIMP1) overexpression in CHO cells can also inhibit cell growth and increase product titers and qP . Given the similar responses, this study evaluated the individual and combined effects of BLIMP1 expression, low temperature, and NaBu treatment on culture performance, cell metabolism, and recombinant protein production of CHO cells. As expected, all three interventions decreased cell growth, arrested cells in G1/G0 cell cycle phase, and increased qP . However, CHO cells presented different responses when considering cell viability, recombinant gene expression, and cell metabolism that indicated differences in the molecular loci by which BLIMP1 and GICs generated higher productivities. Combinations of BLIMP1 expression and GICs acted synergistically to inhibit cell growth and maximize r-protein production, with the BLIMP1/NaBu condition leading to the most significant improvements in product titers and qP . This latter condition also proved to substantially increase product yields (up to 9.8 g immunoglobulin G1 [IgG1]/L and 2.2 g erythropoietin-Fc [EPO-Fc]/L) and qP (up to 179 pg/cell/day [pcd] for IgG1 and 30 pcd for EPO-Fc) in high-density perfusion cultures. These findings offered mechanistic insights about the productivity-enhancing effects of BLIMP1 and GICs, as well as their complementarity for generating highly productive processes.


Asunto(s)
Técnicas de Cultivo Celular por Lotes/métodos , Ingeniería Celular/métodos , Proteínas Recombinantes , Animales , Ácido Butírico/química , Células CHO , Proliferación Celular/genética , Supervivencia Celular , Cricetinae , Cricetulus , Medios de Cultivo , Metabolómica/métodos , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Proteínas Recombinantes/análisis , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
3.
Food Chem Toxicol ; 159: 112743, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34890760

RESUMEN

The prevalence of high-fat diet consumption-related disorders is increasing, and it is often associated with oxidative stress, inflammation, and dysregulation in the brain may lead to neurodegenerative diseases (NDDs). Our study aims to evaluate the neuroprotective effects of sodium butyrate (NaB) on HFD-fed mice. In this study, four-week-old male C57Bl/6NTac mice were divided into three groups; the control group, the HFD group, and the HFD + NaB group where mice received 11 mg/kg body weight of NaB with HFD. Western blotting, reverse transcription-PCR, and ELISA were used for biochemical analysis of brain specimens. We found that NaB restored bodyweight and attenuated P-53, Bcl-2-associated X protein (BAX), and caspase cascades in the brains of HFD-fed mice. In addition. NaB reduced the expressions of proinflammatory cytokines and positively modulated antioxidant biomarkers. NaB treatment upregulated the expression of the growth factor-related factors PPARγ, CREB, and BDNF in the brain tissues of HFD-fed mice. Furthermore, we found that NaB significantly ameliorated glucocorticoid receptor and NLRP3 inflammasome expression. Based on our findings, NaB suppressed apoptotic and inflammatory cytokines and enhanced the expression of endogenous antioxidants in brain tissues of HFD-fed mice. Our data strongly suggests that NaB could be utilized as an effective therapeutic agent for NDDs.


Asunto(s)
Antiinflamatorios , Ácido Butírico , Dieta Alta en Grasa/efectos adversos , Fármacos Neuroprotectores , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Ácido Butírico/química , Ácido Butírico/farmacología , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos
4.
Molecules ; 26(16)2021 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-34443600

RESUMEN

Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (1H, 13C and 119Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric environment similar to ester. FTIR and NMR findings confirm this structure both in solid state and solution. The antitumor efficacy of the triorganotin(IV) butyrates was tested in colon cancer cells and, among them, tributyltin(IV) butyrate (BT2) was selected as the most efficacious. BT2 induced G2/M cell cycle arrest, ER stress, and apoptotic cell death. These effects were obtained using low concentrations of BT2 up to 1 µM, whereas butyric acid alone was completely inefficacious, and the parent compound TBT was poorly effective at the same treatment conditions. To assess whether butyrate in the coordinated form maintains its epigenetic effects, histone acetylation was evaluated and a dramatic decrease in acetyl-H3 and -H4 histones was found. In contrast, butyrate alone stimulated histone acetylation at a higher concentration (5 mM). BT2 was also capable of preventing histone acetylation induced by SAHA, another potent HDAC inhibitor, thus suggesting that it may activate HDACs. These results support a potential use of BT2, a novel epigenetic modulator, in colon cancer treatment.


Asunto(s)
Apoptosis/genética , Ácido Butírico/química , Neoplasias del Colon/patología , Estrés del Retículo Endoplásmico/genética , Epigénesis Genética/efectos de los fármacos , Compuestos de Trialquiltina/química , Compuestos de Trialquiltina/farmacología , Acetilación/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Estrés del Retículo Endoplásmico/efectos de los fármacos , Histona Desacetilasas/metabolismo , Humanos , Procesamiento Proteico-Postraduccional/efectos de los fármacos
5.
Sci Rep ; 11(1): 17298, 2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-34453080

RESUMEN

We investigated the effects of low and high doses of ß-conglycinin and the ameliorative effects of sodium butyrate (based on high-dose ß-conglycinin) on the growth performance, serum immunity, distal intestinal histopathology, and gene, protein expression related to intestinal health in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). The results revealed that the instantaneous growth rate (IGR) of grouper significantly increased, decreased, and increased in the low-dose ß-conglycinin (bL), high-level ß-conglycinin (bH) and high-level ß-conglycinin plus sodium butyrate (bH-NaB), respectively. The feed coefficient ratio (FCR) was significantly increased in the bH and bH-NaB, serum levels of IFN-γ, IL-1ß, and TNF-α were upregulated in the bH. The intestinal diameter/fold height ratio was significantly increased in the bH. Furthermore, there were increases in nitric oxide (NO), total nitric oxide synthase (total NOS), and peroxynitrite anion (ONOO-) in the bH, and decreases in total NOS and ONOO- in the bH-NaB. In the distal intestine, IL-1ß and TGF-ß1 mRNA levels were downregulated and upregulated, respective in the bL. The mRNA levels of TNF-α and IL-6 were upregulated in the bH, and downregulated in the bH-NaB, respectively. Occludin, claudin3 and ZO-3 mRNA levels were upregulated in the bL, downregulated in the bH and then upregulated in the bH-NaB. No significant differences were observed in the mRNA levels of IFN-γ and jam4. And the p-PI3K p85Tyr458/total PI3K p85 value was significantly increased in the bH and then decreased in the bH-NaB, and the total Akt value was significantly increased in the bH. These indicate ß-conglycinin has a regulatory effect on serum immunity and affect distal intestinal development by modulating distal intestinal injury-related parameters. Within the distal intestinal tract, low- and high-dose ß-conglycinin differentially affect immune responses and tight junctions in the distal intestine, which eventually manifests as a reduction in growth performance. Supplementing feed with sodium butyrate might represent an effective approach for enhancing serum immunity, and protects the intestines from damage caused by high-dose ß-conglycinin.


Asunto(s)
Antígenos de Plantas/química , Ácido Butírico/química , Suplementos Dietéticos/análisis , Globulinas/química , Proteínas de Almacenamiento de Semillas/química , Proteínas de Soja/química , Alimentación Animal , Animales , Antígenos de Plantas/metabolismo , Lubina , Ácido Butírico/metabolismo , Claudina-3/genética , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica , Globulinas/metabolismo , Humanos , Inmunidad Innata , Interleucina-6/genética , Intestinos , ARN Mensajero , Proteínas de Almacenamiento de Semillas/metabolismo , Transducción de Señal , Proteínas de Soja/metabolismo , Factor de Necrosis Tumoral alfa/genética , Proteínas de la Zonula Occludens/genética
6.
Molecules ; 26(11)2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34200454

RESUMEN

The current understanding of deviations of human microbiota caused by antibiotic treatment is poor. In an attempt to improve it, a proof-of-principle spectroscopic study of the breath of one volunteer affected by a course of antibiotics for Helicobacter pylori eradication was performed. Fourier transform spectroscopy enabled searching for the absorption spectral structures sensitive to the treatment in the entire mid-infrared region. Two spectral ranges were found where the corresponding structures strongly correlated with the beginning and end of the treatment. The structures were identified as methyl ester of butyric acid and ethyl ester of pyruvic acid. Both acids generated by bacteria in the gut are involved in fundamental processes of human metabolism. Being confirmed by other studies, measurement of the methyl butyrate deviation could be a promising way for monitoring acute gastritis and anti-Helicobacter pylori antibiotic treatment.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Antibacterianos/química , Ácido Butírico/química , Ésteres/química , Gastritis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Ácido Pirúvico/química , Espectrofotometría Infrarroja/métodos
7.
J Photochem Photobiol B ; 216: 112131, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33517071

RESUMEN

Cryptococcus is a globally distributed fungal pathogen that primarily afflicts immunocompromised individuals. The therapeutic options are limited and include mostly amphotericin B or fluconazole, alone or in combination. The extensive usage of antifungals allowed the selection of resistant pathogens posing threats to global public health. Histone deacetylase genes are involved in Cryptococcus virulence, and in pathogenicity and resistance to azoles in Candida albicans. Aiming to assess whether histone deacetylase genes are involved in antifungal response and in synergistic drug interactions, we evaluated the activity of amphotericin B, fluconazole, sulfamethoxazole, sodium butyrate or trichostatin A (histone deacetylase inhibitors), and hydralazine or 5- aza-2'-deoxycytidine (DNA methyl-transferase inhibitors) against different Cryptococcus neoformans strains, C. neoformans histone deacetylase null mutants and Cryptococcus gattii NIH198. The drugs were employed alone or in different combinations. Fungal growth after photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion, alone or in combination with the aforementioned drugs, was assessed for the C. neoformans HDAC null mutant strains. Our results showed that fluconazole was synergistic with sodium butyrate or with trichostatin A for the hda1Δ/hos2Δ double mutant strain. Sulfamethoxazole was synergistic with sodium butyrate or with hydralazine also for hda1Δ/hos2Δ. These results clearly indicate a link between HDAC impairment and drug sensitivity. Photodynamic therapy efficacy on controlling the growth of the HDAC mutant strains was increased by amphotericin B, fluconazole, sodium butyrate or hydralazine. This is the first study in Cryptococcus highlighting the combined effects of antifungal drugs, histone deacetylase or DNA methyltransferase inhibitors and photodynamic therapy in vitro.


Asunto(s)
Antifúngicos/metabolismo , Proteínas Bacterianas/genética , Criptococosis/tratamiento farmacológico , Cryptococcus neoformans/enzimología , Epigénesis Genética/efectos de los fármacos , Histona Desacetilasas/genética , Indoles/metabolismo , Compuestos Organometálicos/metabolismo , Fotoquimioterapia/métodos , Anfotericina B/química , Ácido Butírico/química , Sinergismo Farmacológico , Emulsiones/química , Fluconazol/química , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Humanos , Ácidos Hidroxámicos/química , Indoles/farmacología , Nanopartículas/química , Compuestos Organometálicos/farmacología , Sulfametoxazol/química
8.
Anal Sci ; 37(2): 229-232, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33390466

RESUMEN

The electrorotation (ROT) rates of K562 cells accompanied by erythroid differentiation were estimated to identify the differentiation status by using a novel electrorotation device with a microwell arranged on polynomial electrodes. Successive estimations of individual cells were achieved by sequential manipulations which involve trapping of the cell by positive dielectrophoresis (DEP), rotating by ROT, and removing by negative DEP. The ROT rate increased with the differentiation of K562 cells, because the cytoplasm conductivity would increase with an increase of the concentration of iron ions to produce hemoglobin. The ROT rate could be utilized to estimate the stage of cell differentiation without labeling.


Asunto(s)
Ácido Butírico/farmacología , Técnicas Electroquímicas , Células Eritroides/efectos de los fármacos , Ácido Butírico/química , Diferenciación Celular/efectos de los fármacos , Conductividad Eléctrica , Humanos , Células K562
9.
ACS Appl Bio Mater ; 4(3): 2335-2341, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35014354

RESUMEN

Butyrate has been attracting attention for the suppression of inflammatory bowel disease (IBD). However, clinical trials of butyrate for IBD treatment have resulted in controversial outcomes, likely owing to the adverse effect of butyrate on the intestinal epithelium that was observed at high butyrate concentrations. Herein, we propose polyvinyl butyrate (PVBu) nanoparticles (NPs) as butyrate donors for delivery to the lower part of the intestine for the treatment of colitis. The PVBu NPs suppressed the inflammatory activation of macrophages in vitro, although sodium butyrate inversely further activated macrophages. Oral administration of NPs did not change the luminal concentration of free butyrate; however, NPs showed a therapeutic effect on a colitis mouse model. In addition, incorporation of vitamin D3 into the NPs enhanced the therapeutic effect on colitis. Hence, PVBu NPs are a promising therapeutic for IBD treatment, not only as a butyrate donor but also as a carrier for hydrophobic drugs like vitamin D3.


Asunto(s)
Materiales Biocompatibles/uso terapéutico , Ácido Butírico/uso terapéutico , Colitis/tratamiento farmacológico , Nanopartículas/química , Polivinilos/uso terapéutico , Animales , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Ácido Butírico/química , Células Cultivadas , Colitis/inducido químicamente , Sulfato de Dextran , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Tamaño de la Partícula , Polivinilos/síntesis química , Polivinilos/química , Células RAW 264.7
10.
Int J Mol Sci ; 21(22)2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33187164

RESUMEN

Combined treatments which use nanoparticles and drugs could be a synergistic strategy for the treatment of a variety of cancers to overcome drug resistance, low efficacy, and high-dose-induced systemic toxicity. In this study, the effects on human colon adenocarcinoma cells of surface modified Fe3O4 magnetic nanoparticles (MNPs) in combination with sodium butyrate (NaBu), added as a free formulation, were examined demonstrating that the co-delivery produced a cytotoxic effect on malignant cells. Two different MNP coatings were investigated: a simple polyethylene glycol (PEG) layer and a mixed folic acid (FA) and PEG layer. Our results demonstrated that MNPs with FA (FA-PEG@MNPs) have a better cellular uptake than the ones without FA (PEG@MNPs), probably due to the presence of folate that acts as an activator of folate receptors (FRs) expression. However, in the presence of NaBu, the difference between the two types of MNPs was reduced. These similar behaviors for both MNPs likely occurred because of the differentiation induced by butyrate that increases the uptake of ferromagnetic nanoparticles. Moreover, we observed a strong decrease of cell viability in a NaBu dose-dependent manner. Taking into account these results, the cooperation of multifunctional MNPs with NaBu, taking into consideration the particular cancer-cell properties, can be a valuable tool for future cancer treatment.


Asunto(s)
Antineoplásicos/química , Ácido Butírico/química , Compuestos Férricos/química , Ácido Fólico/química , Nanopartículas de Magnetita/química , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Antineoplásicos/farmacología , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Receptores de Folato Anclados a GPI/metabolismo , Humanos , Magnetismo/métodos , Polietilenglicoles/química
11.
J Mater Chem B ; 8(47): 10739-10743, 2020 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-33103709

RESUMEN

We have successfully fabricated a nanocomposite, which is composed of polyaniline (PAni) and pyrene butyric acid (Pyba) via a solvent shift method, which was self-doped at a neutral pH value. This PAni nanocomposite can act as a fine nanoagent expressing absorbance, fluorescence, and Raman properties according to the surrounding pH values.


Asunto(s)
Compuestos de Anilina/química , Compuestos de Anilina/farmacología , Supervivencia Celular/efectos de los fármacos , Nanocompuestos/química , Compuestos de Anilina/metabolismo , Ácido Butírico/química , Ácido Butírico/metabolismo , Ácido Butírico/farmacología , Línea Celular Tumoral , Supervivencia Celular/fisiología , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Oxidación-Reducción/efectos de los fármacos , Polisorbatos/química , Polisorbatos/metabolismo , Polisorbatos/farmacología
12.
Molecules ; 25(20)2020 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-33080809

RESUMEN

Fermented alcoholic drinks' contribution to the gut microbiota composition is mostly unknown. However, intestinal microorganisms can use compounds present in beer. This work explored the associations between moderate consumption of beer, microbiota composition, and short chain fatty acid (SCFA) profile. Seventy eight subjects were selected from a 261 healthy adult cohort on the basis of their alcohol consumption pattern. Two groups were compared: (1) abstainers or occasional consumption (ABS) (n = 44; <1.5 alcohol g/day), and (2) beer consumption ≥70% of total alcohol (BEER) (n = 34; 200 to 600 mL 5% vol. beer/day; <15 mL 13% vol. wine/day; <15 mL 40% vol. spirits/day). Gut microbiota composition (16S rRNA gene sequencing) and SCFA concentration were analyzed in fecal samples. No differences were found in α and ß diversity between groups. The relative abundance of gut bacteria showed that Clostridiaceae was lower (p = 0.009), while Blautia and Pseudobutyrivibrio were higher (p = 0.044 and p = 0.037, respectively) in BEER versus ABS. In addition, Alkaliphilus, in men, showed lower abundance in BEER than in ABS (p = 0.025). Butyric acid was higher in BEER than in ABS (p = 0.032), and correlated with Pseudobutyrivibrio abundance. In conclusion, the changes observed in a few taxa, and the higher butyric acid concentration in consumers versus non-consumers of beer, suggest a potentially beneficial effect of moderate beer consumption on intestinal health.


Asunto(s)
Bebidas Alcohólicas/microbiología , Cerveza/microbiología , Ácidos Grasos Volátiles/genética , Microbioma Gastrointestinal/genética , Adulto , Bebidas Alcohólicas/efectos adversos , Ácido Butírico/química , Ácido Butírico/metabolismo , Ácidos Grasos Volátiles/metabolismo , Femenino , Humanos , Masculino , Polifenoles/química , ARN Ribosómico 16S/genética
13.
Bioorg Chem ; 104: 104214, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32927128

RESUMEN

In this paper, we study the activity and specificity of EstDZ2, a new thermostable carboxyl esterase of unknown function, which was isolated from a metagenome library from a Russian hot spring. The biocatalytic reaction employing EstDZ2 proved to be an efficient method for the hydrolysis of aryl p-, o- or m-substituted esters of butyric acid and esters of secondary alcohols. Docking studies revealed structural features of the enzyme that led to activity differences among the different substrates.


Asunto(s)
Esterasas/metabolismo , Temperatura , Alcoholes/química , Alcoholes/metabolismo , Biocatálisis , Ácido Butírico/química , Ácido Butírico/metabolismo , Esterasas/química , Esterasas/aislamiento & purificación , Biblioteca de Genes , Manantiales de Aguas Termales , Hidrólisis , Simulación del Acoplamiento Molecular , Estructura Molecular
14.
Eur J Med Chem ; 205: 112616, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32949920

RESUMEN

Based on the SAR of both α1-AR antagonists and 5α-reductase (5AR) inhibitors, the dual-acting agent 4-(1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-1H-indol-3-yl)butanoic acid 4aaa was designed against BPH and synthesized by two steps of N-alkylation. One-pot protocol towards 4aaa was newly developed. With IL [C6min]Br as solvent, the yield of 4aaa was increased to 75.1% from 16.0% and the reaction time was shortened in 1.5 h from 48 h. 25 derivatives structurally based on arylpiperazine and indolyl butyric acid with alkyl linker were prepared. The protocol was futher extended to get another 14 derivatives wherein O-alkylation was involved, and applied to the synthesis of biologically efficient molecules DPQ and Aripiprazole. Expectedly, compound 4aaa exhibited dual inhibition of α1-AR and 5α-reductase, and exhibited no obvious cytotoxicity against human cells. The pharmacokinetic properties of 4aaa was also determined.


Asunto(s)
Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/farmacología , Líquidos Iónicos/química , Hiperplasia Prostática/tratamiento farmacológico , Antagonistas de Receptores Androgénicos/síntesis química , Antagonistas de Receptores Androgénicos/química , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/uso terapéutico , Ácido Butírico/química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/uso terapéutico , Técnicas de Química Sintética , Humanos , Masculino , Receptores Androgénicos/metabolismo
15.
ACS Synth Biol ; 9(9): 2390-2398, 2020 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-32813973

RESUMEN

n-Butanol is often considered a potential substitute for gasoline due to its physicochemical properties being closely related to those of gasoline. In this study, we extend our earlier work to convert endogenously producing butyrate via the FASII pathway using thioesterase TesBT to its corresponding alcohol, i.e., butanol. We first assembled pathway genes, i.e., car encoding carboxylic acid reductase from Mycobacterium marinum, sfp encoding phosphopantetheinyl transferase from Bacillus subtilis, and adh2 encoding alcohol dehydrogenase from S. cerevisiae, responsible for bioconversion of butyrate to butanol in three different configurations (Operon, Pseudo-Operon, and Monocistronic) to achieve optimum expression of each gene and compared with the clostridial solventogenic pathway for in vivo conversion of butyrate to butanol under aerobic conditions. An E. coli strain harboring car, sfp, and adh2 in pseudo-operon configuration was able to convert butyrate to butanol with 100% bioconversion efficiency when supplemented with 1 g/L of butyrate. Further, co-cultivation of an upstream strain (butyrate-producing) with a downstream strain (butyrate to butanol converting) at different inoculation ratios was investigated, and an optimized ratio of 1:4 (upstream strain: downstream strain) was found to produce ∼2 g/L butanol under fed-batch fermentation. Further, a mono-cultivation approach was applied by transforming a plasmid harboring tesBT gene into the downstream strain. This approach produced 0.42 g/L in a test tube and ∼2.9 g/L butanol under fed-batch fermentation. This is the first report where both mono- and co-cultivation approaches were tested and compared for butanol production, and butanol titers achieved using both strategies are the highest reported values in recombinant E. coli utilizing FASII pathway.


Asunto(s)
1-Butanol/metabolismo , Vías Biosintéticas/genética , Escherichia coli/química , Ingeniería Metabólica/métodos , 1-Butanol/química , Alcohol Deshidrogenasa/genética , Proteínas Bacterianas/genética , Técnicas de Cultivo Celular por Lotes , Ácido Butírico/química , Ácido Butírico/metabolismo , Escherichia coli/metabolismo , Ácidos Grasos/biosíntesis , Proteínas Fúngicas/genética , Oxidorreductasas/genética , Plásmidos/genética , Plásmidos/metabolismo , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genética
16.
Biosci Biotechnol Biochem ; 84(8): 1541-1545, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32419623

RESUMEN

The volatile components emitted from two scale insects, Ceroplastes japonicus and Ceroplastes rubens, were identified using GC-MS analysis. The major volatile components of the solvent extract from C. japonicus were α-humulene (35.8%) and δ-cadinene (17.0%), while those of C. rubens were ß-selinene (10.3%) and ß-elemene (5.1%). In GC/olfactometry, linalool, butyric acid, 3-methylbutyric acid, 2-methylbutyric acid, and vanillin were identified as the odor-active components of the extract from C. japonicus, in addition to trace amounts of trans-4,5-epoxy-(2E)-decenal, 4-methyl-(3E)-hexenoic acid, and phenylacetic acid. With regard to C. rubens, trans-4,5-epoxy-(2E)-decenal, 3-methylbutyric acid, and phenylacetic acid were identified as the odor-active components. Besides, decan-1,4-olide (γ-decalactone) with milky cherry-like note and 3-hydroxy-4,5-dimethylfuran-2(5H)-one (sotolone) with brown sugar-like note were also detected as the characteristic cherry-like sweet-and-sour note of these two scale insects. ABBREVIATIONS: GC: Gas chromatography; GC/O: gas chromatography/olfactometry.


Asunto(s)
Hemípteros/química , Odorantes/análisis , Olfato/fisiología , Compuestos Orgánicos Volátiles/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/aislamiento & purificación , Aldehídos/química , Aldehídos/aislamiento & purificación , Animales , Benzaldehídos/química , Benzaldehídos/aislamiento & purificación , Butiratos/química , Butiratos/aislamiento & purificación , Ácido Butírico/química , Ácido Butírico/aislamiento & purificación , Caproatos/química , Caproatos/aislamiento & purificación , Compuestos Epoxi/química , Compuestos Epoxi/aislamiento & purificación , Furanos/química , Furanos/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , Hemípteros/fisiología , Hemiterpenos/química , Hemiterpenos/aislamiento & purificación , Lactonas/química , Lactonas/aislamiento & purificación , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/aislamiento & purificación , Ácidos Pentanoicos/química , Ácidos Pentanoicos/aislamiento & purificación , Fenilacetatos/química , Fenilacetatos/aislamiento & purificación , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/aislamiento & purificación , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/aislamiento & purificación , Tetrahidronaftalenos/química , Tetrahidronaftalenos/aislamiento & purificación , Compuestos Orgánicos Volátiles/clasificación , Compuestos Orgánicos Volátiles/aislamiento & purificación
17.
J Labelled Comp Radiopharm ; 63(10): 442-455, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32472945

RESUMEN

The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic µPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 µM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.


Asunto(s)
Ácido Butírico/química , Ácido Butírico/síntesis química , Tomografía de Emisión de Positrones , Animales , Ácido Butírico/farmacología , Línea Celular Tumoral , Masculino , Ratones , Ratas
18.
Carbohydr Polym ; 237: 116174, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32241452

RESUMEN

Hydroxyapatite-associated bacterial cellulose (BC/HA) is a promising composite for biomedical applications. However, this hybrid composite has some limitations due to its low in vivo degradability. The objective of this work was to oxidize BC and BC/HA composites for different time periods to produce 2,3 dialdehyde cellulose (DAC). The BC and oxidized BC (OxBC) membranes were mineralized to obtain the hybrid materials (BC/HA and OxBC/HA) and their physico-chemical, degradability, and bioactivity properties were studied. The results showed that OxBC/HA was more bioactive and degradable than BC/HA, which isa function of the degree of BC oxidation. High glucose levels in the BC degradation were observed as a function of oxidation degree, and other products, such as butyric acid and acetic acid resulted from DAC degradation. Therefore, this chemical modification reaction favors BC degradation, making it a good biodegradable and bioactive material with a potential for bone regeneration applications.


Asunto(s)
Celulosa/química , Durapatita/química , Ácido Acético/química , Acetobacteraceae , Líquidos Corporales/química , Regeneración Ósea , Ácido Butírico/química , Glucosa/química , Oxidación-Reducción , Ingeniería de Tejidos
19.
Sci Rep ; 10(1): 646, 2020 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-31959807

RESUMEN

In a more synthetical approach to the study of ion-specific phenomena, four dipodal bis(guanidinium) siloxanes have been synthesized starting from glycine, ß-alanine, γ-aminobutanoic acid, L-proline and 1,3-bis(3-aminopropyl)tetramethyldisiloxane. Together with their non-amide progenitor they were comparatively studied in regards to their interactions with nine different anions: sulphate, chromate, molybdate, benzoate, chloride, azide, nitrite, nitrate and thiocyanate. Their aqueous solubilities, form, 1H NMR and FT-IR spectra were examined while searching for anion-specific interactions falling in- or outside of the Hofmeister series. We show that although the "chao-" and "kosmotropic" ions affect the properties of solutions in a predictable way, more selective cation-anion pairing is responsible for phase separation and crystallinity. As a prominent example, crystal structure of one of the benzoate salts was successfully obtained and reveals a synergy of hydrophobic packing, ionic and hydrogen bonding. Immobilized but still flexible siloxane bridges give rise to crystals described by P 42/n space group and neatly segregated into hydro- and lipophilic sections.


Asunto(s)
Aminoácidos/química , Guanidina/síntesis química , Iones/química , Silanos/síntesis química , Aniones/química , Ácido Butírico/química , Cristalización , Glicina/química , Guanidina/química , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Prolina/química , Silanos/química , Solubilidad , Soluciones , Relación Estructura-Actividad , Agua , beta-Alanina/química
20.
Bioprocess Biosyst Eng ; 43(2): 273-282, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31595329

RESUMEN

Structured lipids (SLs) rich in conjugated linoleic acid (CLA) and butyric acid with functions of low calorie and weight loss were synthesized in this study. By comparison of different synthetic routes, transesterification of CLA ethyl ester (CLAee) and tributyrin under vacuum was determined as the best method. The reaction conditions for SL synthesis were screened and the best conditions were as follows: Novozym 435 as the catalyst, enzyme load 6 wt%, temperature 60 °C, substrate molar ratio 2:1 (CLAee/tributyrin), water activity 0.68, reaction time 80 min. Under these conditions, the final product contained 97.5% of SLs, in which the contents of dibutyl-conjugated linoleoyl-glycerol and butyl-diconjugated linoleoyl-glycerol were 78.4% and 19.1%, respectively. The reusability evaluation indicated that the lipase could be reused at least 17 times. The obtained SLs with functions of both fatty acids could replace natural oil in food for inhibition of obesity and thus have great potential for commercial applications.


Asunto(s)
Ácido Butírico/química , Ácido Linoleico/química , Lipasa/química , Lípidos , Enzimas Inmovilizadas , Proteínas Fúngicas , Lípidos/síntesis química , Lípidos/química
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