Isothiocyanates

异硫氰酸酯
  • 文章类型: Journal Article
    这项研究试图开发2种含有Salvadorapersica(miswak)或异硫氰酸苄酯(BITC)提取物的可生物降解的牙周芯片,并评估其在治疗牙周炎中的临床有效性。
    这项临床试验是在牙科学院进行的,TeknologiMARAShahAlam大学,Selangor,马来西亚,从2010年9月到2012年4月。使用S.persica配制牙周芯片,异硫氰酸苄酯(BITC)和壳聚糖提取物。所有患者均在基线时接受全口刮削和根部平整治疗。此后,将牙周袋(长度≥5mm)分为4组:对照组;第2组(普通壳聚糖芯片);第3组(S。桃提取物);和第4组(BITC提取物)。斑块指数(PI),探查出血(BOP),仅在第0天和第60天记录牙周探诊袋深度和临床附着水平。
    共有12名患者参加了这项研究。总的来说,评价240个牙周袋。这项研究揭示了PI的显着改善,4组均有BOP和牙周袋深度减少(P<0.05)。与对照组和其他芯片治疗组相比,接受S.persica芯片的组的临床附着水平的改善明显更高(P<0.001)。
    含有S.persica的牙周芯片可用作辅助治疗牙周炎患者。
    UNASSIGNED: This study attempted to develop 2 biodegradable periodontal chips containing Salvadora persica (miswak) or benzyl isothiocyanate (BITC) extracts and evaluate their clinical effectiveness in managing periodontitis.
    UNASSIGNED: This clinical trial was conducted at the Faculty of Dentistry, Universiti Teknologi MARA Shah Alam, Selangor, Malaysia, from September 2010 to April 2012. Periodontal chips were formulated using S. persica, benzyl isothiocyanate (BITC) and chitosan extracts. All patients were treated with full mouth scaling and root planing at baseline. Thereafter, the periodontal pockets (≥5 mm in length) were divided into 4 groups: the control group; group 2 (plain chitosan chip); group 3 (S. persica extract); and group 4 (BITC extract). Plaque index (PI), bleeding on probing (BOP), periodontal probing pocket depth and clinical attachment levels were recorded at days 0 and 60 only.
    UNASSIGNED: A total of 12 patients participated in this study. Overall, 240 periodontal pockets were evaluated. The study revealed significant improvements in PI, BOP and reduction in periodontal pocket depth in all 4 groups (P <0.05). The improvement in clinical attachment level was significantly higher (P <0.001) among the group that received S. persica chips compared to the control and other chip-treated groups.
    UNASSIGNED: Periodontal chips containing S. persica can be used as adjuncts to treat patients with periodontitis.
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  • 文章类型: Journal Article
    通常用于食品制备的商业芥末糊剂含有化学感觉异硫氰酸盐(ITC)的同源化合物,其在食用时引起刺激性感觉。从未研究过嗅闻饮食酒精饮料对芥末辣味感的影响。虽然大多数感官评价研究分别关注单个食品和饮料,缺乏对食用芥末时嗅酒的嗅觉研究。这里,开发了一种方法,该方法结合了动物行为研究和卷积神经网络的使用,以分析小鼠同时嗅酒和食用芥末时的面部表情。结果表明,经过训练和验证的深度学习模型可识别29%的图像,这些图像描绘了山葵和酒精的共同治疗,属于山葵阴性酒阳性组的类别,而无需进行先前的训练材料过滤。从所选择的视频帧图像获得的小鼠鬼脸量表得分的统计学分析揭示了存在和不存在液体之间的显著差异(P<0.01)。这一发现表明,饮食酒精饮料可能对小鼠山葵引起的反应具有减弱的作用。这种组合方法具有未来个体ITC化合物筛选和精神成分感官分析的潜力。然而,需要进一步研究以研究酒精诱导的芥末辣味抑制的潜在机制。
    The commercial wasabi pastes commonly used for food preparation contain a homologous compound of chemosensory isothiocyanates (ITCs) that elicit an irritating sensation upon consumption. The impact of sniffing dietary alcoholic beverages on the sensation of wasabi spiciness has never been studied. While most sensory evaluation studies focus on individual food and beverages separately, there is a lack of research on the olfactory study of sniffing liquor while consuming wasabi. Here, a methodology is developed that combines the use of an animal behavioral study and a convolutional neural network to analyze the facial expressions of mice when they simultaneously sniff liquor and consume wasabi. The results demonstrate that the trained and validated deep learning model recognizes 29% of the images depicting co-treatment of wasabi and alcohol belonging to the class of the wasabi-negative liquor-positive group without the need for prior training materials filtering. Statistical analysis of mouse grimace scale scores obtained from the selected video frame images reveals a significant difference (P < 0.01) between the presence and absence of liquor. This finding suggests that dietary alcoholic beverages might have a diminishing effect on the wasabi-elicited reactions in mice. This combinatory methodology holds potential for individual ITC compound screening and sensory analyses of spirit components in the future. However, further study is required to investigate the underlying mechanism of alcohol-induced suppression of wasabi pungency.
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  • 文章类型: Journal Article
    萝卜硫素被认为是西兰花芽饮食消费后的葡萄糖硫素的生物活性代谢产物。尽管这两种分子都以稳定的形式通过肠腔进入大肠,它们对第一肠道的生物学影响描述甚少。在乳糜泻患者中,小肠的功能受到乳糜泻(CD)的影响,其严重结局由无麸质饮食方案控制。然而,炎症和氧化应激的病理征象可能持续存在.这项研究的目的是在麦醇溶蛋白诱导的炎症的细胞模型中比较萝卜硫素与其前体葡萄糖苷的生物活性。人肠上皮细胞(CaCo-2)用促炎细胞因子(IFN-γ,IL-1β)和体外消化的麦醇溶蛋白,而氧化应激是由H2O2诱导的。LC-MS/MS分析证实西兰花芽中的萝卜硫烷在模拟胃肠消化后是稳定的。它抑制了所有选择作为炎症读数的趋化因子的释放,对MCP-1具有更有效的作用(IC50=7.81µM)。相反,葡萄糖苷(50µM)无活性。这些分子无法抵消对DNA(γ-H2AX)和过氧化氢酶水平的氧化损伤;然而,NF-κB和Nrf-2的活性受两种分子的调节。还在Transwell®模型中评估了对上皮通透性(TEER)的影响。在包括麦醇溶蛋白的促炎组合的情况下,TEER值既不是通过萝卜硫烷也不是通过葡硫烷恢复的。相反,在与活化巨噬细胞(THP-1)共培养的情况下,萝卜硫烷仅抑制MCP-1(IC50=20.60µM)和IL-1β(IC50=1.50µM)的释放,但这两种分子在50μM时恢复了上皮完整性。我们的工作表明,葡糖硫素不应该仅仅被认为是小肠水平的惰性前体,因此表明对裁谈会框架的潜在兴趣。它的生物活性可能意味着,至少在某种程度上,分子机制不同于萝卜硫烷。
    Sulforaphane is considered the bioactive metabolite of glucoraphanin after dietary consumption of broccoli sprouts. Although both molecules pass through the gut lumen to the large intestine in stable form, their biological impact on the first intestinal tract is poorly described. In celiac patients, the function of the small intestine is affected by celiac disease (CD), whose severe outcomes are controlled by gluten-free dietary protocols. Nevertheless, pathological signs of inflammation and oxidative stress may persist. The aim of this study was to compare the biological activity of sulforaphane with its precursor glucoraphanin in a cellular model of gliadin-induced inflammation. Human intestinal epithelial cells (CaCo-2) were stimulated with a pro-inflammatory combination of cytokines (IFN-γ, IL-1β) and in-vitro-digested gliadin, while oxidative stress was induced by H2O2. LC-MS/MS analysis confirmed that sulforaphane from broccoli sprouts was stable after simulated gastrointestinal digestion. It inhibited the release of all chemokines selected as inflammatory read-outs, with a more potent effect against MCP-1 (IC50 = 7.81 µM). On the contrary, glucoraphanin (50 µM) was inactive. The molecules were unable to counteract the oxidative damage to DNA (γ-H2AX) and catalase levels; however, the activity of NF-κB and Nrf-2 was modulated by both molecules. The impact on epithelial permeability (TEER) was also evaluated in a Transwell® model. In the context of a pro-inflammatory combination including gliadin, TEER values were recovered by neither sulforaphane nor glucoraphanin. Conversely, in the context of co-culture with activated macrophages (THP-1), sulforaphane inhibited the release of MCP-1 (IC50 = 20.60 µM) and IL-1β (IC50 = 1.50 µM) only, but both molecules restored epithelial integrity at 50 µM. Our work suggests that glucoraphanin should not merely be considered as just an inert precursor at the small intestine level, thus suggesting a potential interest in the framework of CD. Its biological activity might imply, at least in part, molecular mechanisms different from sulforaphane.
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  • 文章类型: Journal Article
    在这里,我们描述了异硫氰酸酯与多种取代的N-芳基氰基硫甲酰胺以1:1的摩尔比进行的第一个一致的区域特异性反应,以产生一系列修饰有多个官能团的咪唑烷亚氨基二硫酮。该反应在室温下进行,使用20mol%催化量的三乙胺和DMF作为溶剂,以排他性区域选择性选择性地形成所述产物。该方法具有广泛的底物范围,不需要色谱,和良好的高反应产率。通过简单的乙醚/盐水萃取分离产物,并通过多核NMR光谱和高精度质量测量验证结构。通过单晶X射线衍射分析建立了观察到的区域异构体的第一个结论性分子结构阐明。同样,通过X射线衍射分析证明了N-芳基氰基硫代甲酰胺反应物的互变异构体。在隐式DMF溶剂中进行B3LYP-D4/def2-TZVP水平的密度泛函理论计算以支持所述区域化学结果和提出的机理。
    Herein, we describe the first consistent regiospecific reaction of isothiocyanates with a variety of substituted N-arylcyanothioformamides in a 1:1 molar ratio to generate a series of imidazolidineiminodithiones decorated with a multitude of functional groups on both aromatic rings. The reaction is carried out at room temperature using a 20 mol% catalytic amount of triethylamine with DMF as the solvent to selectively form the mentioned products with exclusive regioselectivity. The methodology features wide substrate scope, no requirement for chromatography, and good to high reaction yields. The products were isolated by simple ether/brine extraction and the structures were verified by multinuclear NMR spectroscopy and high accuracy mass measurements. The first conclusive molecular structure elucidation of the observed regioisomer was established by single-crystal X-ray diffraction analysis. Likewise, the tautomer of the N-arylcyanothioformamide reactant was proven by X-ray diffraction analysis. Density functional theory computations at the B3LYP-D4/def2-TZVP level in implicit DMF solvent were conducted to support the noted regiochemical outcome and proposed mechanism.
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  • 文章类型: Journal Article
    生物熏蒸被提议作为合成农药的替代品,用于农业土壤的消毒。鉴于某些植物物种释放的异硫氰酸酯(ITC)的杀生物作用,就像十字花科.然而,生物熏蒸也存在局限性;因此,一种新颖且可行的替代方法可能是将ITC作为加载到可生物降解的水凝胶中的成分直接引入农业土壤中。因此,在这项工作中,开发了基于ITCs的微乳液,可以将其加载到基于海藻酸钠(ALG)或羧甲基纤维素钠(CMC)的多孔聚合物基水凝胶珠粒中。三个ITC(乙基,苯基,和异硫氰酸烯丙酯)和三种不同的表面活性剂(十二烷基硫酸钠,考虑了Brij35和Tween80)。用衰减ATR-FTIR光谱和差示扫描量热法表征了最佳系统,以研究微乳液/凝胶相互作用如何影响凝胶特性,如平衡水含量或自由水指数。最后,通过紫外-可见分光光度法研究了负载和释放曲线。发现CMC水凝胶珠粒显示相对于ALG珠粒在水中的胶束释放的稍微更有效的分布。出于这个原因,并且由于Fe(III)对其杀生物特性的贡献增强,基于CMC的水凝胶在实际农业土壤上的应用是最有前途的。
    Biofumigation was proposed as an alternative to synthetic pesticides for the disinfection of agricultural soils, in view of the biocidal effect of isothiocyanates (ITCs) released by some vegetal species, like Brassicaceae. However, biofumigation also presents limitations; thus, a novel and viable alternative could be the direct introduction of ITCs into agricultural soils as components loaded into biodegradable hydrogels. Thus, in this work, ITCs-based microemulsions were developed, which can be loaded into porous polymer-based hydrogel beads based on sodium alginate (ALG) or sodium carboxymethyl cellulose (CMC). Three ITCs (ethyl, phenyl, and allyl isothiocyanate) and three different surfactants (sodium dodecylsulfate, Brij 35, and Tween 80) were considered. The optimal system was characterized with attenuated ATR-FTIR spectroscopy and differential scanning calorimetry to study how the microemulsion/gels interaction affects the gel properties, such as the equilibrium water content or free water index. Finally, loading and release profiles were studied by means of UV-Vis spectrophotometry. It was found that CMC hydrogel beads showed a slightly more efficient profile of micelles\' release in water with respect to ALG beads. For this reason, and due to the enhanced contribution of Fe(III) to their biocidal properties, CMC-based hydrogels are the most promising in view of the application on real agricultural soils.
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  • 文章类型: Journal Article
    通过诱导含有H/K-ATPase的小管囊泡向顶膜的运输,发现溶酶体Ca2通道TRPML1负责小鼠胃壁细胞中的胃酸分泌。因此,我们假设TRPML1在永生化人壁细胞系HGT-1中调节质子分泌的作用相似。主要重点是使用已知的合成激动剂ML-SA1和ML-SA5以及拮抗剂ML-SI3研究TRPML1在质子分泌中的参与,此外,以识别靶向通道的食物衍生化合物。拮抗剂ML-SI3使ML-SA1刺激的质子分泌减少了122.2±22.7%。类固醇激素17β-雌二醇,存在于动物源性食品中,ML-SA1的质子分泌效应降低了63.4±14.5%。我们还证明了ML-SA1和ML-SA5对TRPML1敲低细胞的质子分泌作用降低。食物来源的化合物萝卜硫烷和海藻糖可促进HGT-1细胞中的质子分泌,但可能独立于TRPML1起作用。此外,组胺和咖啡因诱导的质子分泌既不受TRPML1拮抗剂ML-SI3的影响,也不受TRPML1敲低的影响。总之,获得的结果表明,TRPML1的激活促进HGT-1细胞中的质子分泌,但该通道可能不参与经典信号通路。
    The lysosomal Ca2+ channel TRPML1 was found to be responsible for gastric acid secretion in murine gastric parietal cells by inducing the trafficking of H+/K+-ATPase containing tubulovesicles to the apical membrane. Therefore, we hypothesized a similar role of TRPML1 in regulating proton secretion in the immortalized human parietal cell line HGT-1. The primary focus was to investigate the involvement of TRPML1 in proton secretion using the known synthetic agonists ML-SA1 and ML-SA5 and the antagonist ML-SI3 and, furthermore, to identify food-derived compounds that target the channel. Proton secretion stimulated by ML-SA1 was reduced by 122.2 ± 22.7% by the antagonist ML-SI3. The steroid hormone 17β-estradiol, present in animal-derived foods, diminished the proton secretory effect of ML-SA1 by 63.4 ± 14.5%. We also demonstrated a reduction in the proton secretory effects of ML-SA1 and ML-SA5 on TRPML1 knock-down cells. The food-derived compounds sulforaphane and trehalose promoted proton secretion in HGT-1 cells but may act independently of TRPML1. Also, histamine- and caffeine-induced proton secretion were affected by neither the TRPML1 antagonist ML-SI3 nor the TRPML1 knock-down. In summary, the results obtained suggest that the activation of TRPML1 promotes proton secretion in HGT-1 cells, but the channel may not participate in canonical signaling pathways.
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  • 文章类型: Journal Article
    阿尔茨海默病(AD)的复杂性为开发有效的干预措施带来了重大障碍。萝卜硫素(SFN)因其抗氧化作用而备受关注,抗炎,和神经保护特性,这可以解决AD病理学的各个方面。本研究探讨了SFN在Aβ(1-42)肽诱导的AD大鼠模型中的潜力。通过将Aβ(1-42)肽直接注射到大鼠的脑室中来触发AD症状。SFN(10mg/kg和20mg/kg),Trigonelline(10mg/kg),在Aβ(1-42)处理的动物中施用吡格列酮(10mg/kg)。使用新型物体识别测试进行行为评估。各种生化参数,如可溶性Aβ(1-42),IRS-S312,GSK-3β,TNF-α,乙酰胆碱酯酶,亚硝酸盐水平,脂质过氧化,谷胱甘肽活性降低,使用ELISA试剂盒和分光光度法进行定量。组织病理学分析包括苏木精和伊红,刚果红,和IRS-1免疫组织化学染色。进行定量以评估神经元损失和Aβ斑块负荷。本研究的新颖性在于其在双剂量下对SFN对多种AD相关通路的影响的综合评价。新型物体识别测试表明,SFN,尤其是在更高的剂量下,改善Aβ(1-42)诱导的记忆缺陷。生物化学,SFN降低海马Aβ水平,IRS-S312,GSK-3β,TNF-α,和乙酰胆碱酯酶活性,在增加谷胱甘肽水平的同时,都是以剂量依赖的方式。组织病理学分析进一步证实了SFN对Aβ诱导的神经元损伤的保护作用,淀粉样变性,和胰岛素信号的变化。这些结果突出了SFN作为AD多方面治疗剂的潜力,由于其抗氧化作用,为治疗提供了一个有希望的途径,抗炎,和神经保护特性。将Trigonelline和吡格列酮与SFN结合使用,可以洞悉潜在的协同作用。这可能为开发AD的联合疗法铺平道路。
    The intricate nature of Alzheimer\'s disease (AD) has presented significant hurdles in the development of effective interventions. Sulforaphane (SFN) is of interest due to its antioxidative, anti-inflammatory, and neuroprotective properties, which could address various aspects of AD pathology. This study explores the potential of SFN in a rat model of AD induced by Aβ (1-42) peptides. AD symptoms were triggered in rats by injecting Aβ (1-42) peptides directly into their cerebral ventricles. SFN (10 mg/kg and 20 mg/kg), Trigonelline (10 mg/kg), and Pioglitazone (10 mg/kg) were administered in Aβ (1-42) treated animals. Behavioral assessments were performed using the Novel Object Recognition tests. Various biochemical parameters, such as soluble Aβ (1-42), IRS-S312, GSK-3β, TNF-α, acetylcholinesterase, nitrite levels, lipid peroxidation, and reduced glutathione activity, were quantified using ELISA kits and spectrophotometric assays. Histopathological analyses included Hematoxylin and Eosin, Crystal Violet, Congo red, and IRS-1 Immunohistochemistry staining. Quantification was performed to assess neuronal loss and Aβ plaque burden. The novelty of this study lies in its comprehensive evaluation of SFN\'s impact on multiple AD-related pathways at dual doses. The Novel Object Recognition test revealed that SFN, especially at higher doses, improved memory deficits induced by Aβ (1-42). Biochemically, SFN reduced hippocampal Aβ levels, IRS-S312, GSK-3β, TNF-α, and acetylcholinesterase activity, while increasing glutathione levels, all in a dose-dependent manner. Histopathological analyses further confirmed SFN\'s protective role against Aβ-induced neuronal damage, amyloidosis, and changes in insulin signaling. These results highlight SFN\'s potential as a multifaceted therapeutic agent for AD, offering a promising avenue for treatment due to its antioxidative, anti-inflammatory, and neuroprotective properties. The inclusion of combination treatments with Trigonelline and Pioglitazone alongside SFN offers insights into potential synergistic effects, which could pave the way for developing combination therapies for AD.
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  • 文章类型: Journal Article
    Microgreens,也被称为超级食品,因为它们的营养含量高,不同的风味特征,和可持续的种植方法,这使得他们的美食和有价值的健康和美味的饮食。本研究调查了十字花科的微绿,提出了一种新的系统(质量指标),允许在它们之间进行评分。14种芸苔属微绿种在形态上,植物化学,并进行了感官调查。形态学评估显示,萝卜微绿表现出最高的叶面积(p<0.05),而红色mizuna表现出优异的产量。花椰菜微绿含有最高浓度的抗坏血酸(HPLC-DAD)和总酚含量(p<0.05)。使用HPLC-MS/MS的植物化学分析鉴定了超过18种芥子油苷和酚类化合物。红芥菜和红甘蓝的芥子油苷含量最高(p<0.05)。豆瓣菜的酚类化合物含量最高(p<0.05),主要是类黄酮,而西兰花和萝卜含有最高的异硫氰酸盐水平。花椰菜微绿是消费者接受最多的品种。应用质量指标评分系统识别萝卜,花椰菜,和西兰花微绿是最有前途的物种。这项研究强调了甘蓝型油菜作为促进健康的植物化学物质的极好来源的潜力,具有良好的市场接受度。为营养研究和商业应用提供有价值的见解。
    Microgreens, also called superfoods, emerge because of their high levels of nutrients, diverse flavour profiles, and sustainable cultivation methods, which make them culinary delights and valuable to a healthy and flavorful diet. The present study investigated Brassicaceae family microgreens, proposing a novel system (quality indices) that allows scoring among them. Fourteen Brassica microgreen species were morphological, phytochemical, and sensorial investigated. The morphological assessment revealed that radish microgreens exhibited the highest leaf area (p < 0.05), while red mizuna demonstrated superior yield. Cauliflower microgreens contained the highest concentrations of ascorbic acid (HPLC-DAD) and total phenolic content (p < 0.05). Phytochemical analysis using HPLC-MS/MS identified over 18 glucosinolates and phenolic compounds. Red mustard and red cabbage showed the highest glucosinolate content (p < 0.05). Watercress exhibited the highest phenolic compound content (p < 0.05), primarily flavonoids, while broccoli and radish contained the highest isothiocyanate levels. Cauliflower microgreens resulted in the most consumer-accepted variety. Appling quality indices scoring system identified radish, cauliflower, and broccoli microgreens as the most promising species. This study underscores the potential of Brassica microgreens as an excellent source of health-promoting phytochemicals with favorable market acceptance, providing valuable insights for both nutritional research and commercial applications.
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  • 文章类型: Journal Article
    从Eutremajaponicum中分离出的异硫氰酸甲基亚磺基己酯(6-MSITC)是治疗乳腺癌的有希望的候选药物,结直肠癌和胃癌,代谢综合征,心脏病,糖尿病,和肥胖,由于其抗炎和抗氧化特性。此外,它的神经保护特性,改善认知功能和保护多巴胺能神经元,使其成为治疗神经退行性疾病如痴呆症的优秀候选药物,老年痴呆症,和帕金森病。6-MSITC作用于许多信号通路,如PPAR,AMPK,PI3K/AKT/mTOR,Nrf2/Keap1-ARE,ERK1/2-ELK1/CHOP/DR5和MAPK。然而,尽管体外和体内动物研究以及一些人体研究取得了非常有希望的结果,该分子尚未在人群中进行彻底测试。尽管如此,芥末应被归类为人类疾病一级和二级预防的“超级食品”。本文回顾了当前关于6-MSITC的最新研究及其潜在的临床应用,详细讨论了该分子激活的信号通路及其相互作用。
    Methylsulfinyl hexyl isothiocyanate (6-MSITC) isolated from Eutrema japonicum is a promising candidate for the treatment of breast cancer, colorectal and stomach cancer, metabolic syndrome, heart diseases, diabetes, and obesity due to its anti-inflammatory and antioxidant properties. Also, its neuroprotective properties, improving cognitive function and protecting dopaminergic neurons, make it an excellent candidate for treating neurodegenerative diseases like dementia, Alzheimer\'s, and Parkinson\'s disease. 6-MSITC acts on many signaling pathways, such as PPAR, AMPK, PI3K/AKT/mTOR, Nrf2/Keap1-ARE, ERK1/2-ELK1/CHOP/DR5, and MAPK. However, despite the very promising results of in vitro and in vivo animal studies and a few human studies, the molecule has not yet been thoroughly tested in the human population. Nonetheless, wasabi should be classified as a \"superfood\" for the primary and secondary prevention of human diseases. This article reviews the current state-of-the-art research on 6-MSITC and its potential clinical uses, discussing in detail the signaling pathways activated by the molecule and their interactions.
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  • 文章类型: Journal Article
    与烯丙基反应-,乙酰-,在3-氨基-4,6-二甲基吡啶-2(1H)-酮的基础上研究了异硫氰酸苯酯,3-氨基-4-苯基吡啶-2-酮,和3-氨基-4-(噻吩-2-基)吡啶-2(1H)-酮(苯甲酰基-)异硫氰酸酯,得到相应的硫脲衍生物8-11a-c。与标准药物阿卡波糖相比,获得了十二种硫脲衍生物,并研究了它们对α-葡萄糖苷酶的抗糖尿病活性。比较药物阿卡波糖在15mM的浓度下抑制α-葡糖苷酶的活性达46.1%(阿卡波糖的IC50为11.96mM)。根据所进行的研究的结果,结果表明,烷基和苯基硫脲衍生物8,9a-c,与它们的乙酰基-(苯甲酰基)衍生物和10,11a-c相反,显示高抗糖尿病活性。因此,1-(4,6-二甲基-2-氧代-1,2-二氢吡啶-3-基)-3-苯基硫脲9a对酶α-葡萄糖苷酶具有最高的抑制活性,超过比较药物阿卡波糖的活性,其在15mm的浓度下抑制α-葡糖苷酶的活性56.6%(IC50=9,77mM)。1-(6-甲基-2-氧代4-(噻吩-2-基)-1,2-二氢吡啶-3-基)-3-苯基硫脲9c对酶α-葡萄糖苷酶具有抑制活性,与比较药物阿卡波糖相当,抑制α-葡萄糖苷酶的活性,浓度为15mm/41.2%(IC50=12,94mM)。化合物8a,8b,和9b显示出抑制酶α-葡萄糖苷酶的活性,与阿卡波糖相比活性较低,抑制浓度为15mM的α-葡萄糖苷酶的活性23.3%,26.9%,和35.2%,分别。化合物8a对α-葡萄糖苷酶的IC50,8b,发现9b为16.64mM,19.79mM,和21.79mM,分别。其他化合物8c,10a,10b,10c,11a,11b,和11c未显示对α-葡糖苷酶的抑制活性。因此,基于3-氨基吡啶-2(1H)-酮的新合成的硫脲衍生物是进一步修饰和研究其潜在抗糖尿病活性的有希望的候选者。这些积极的生物分析结果将刺激进一步深入的研究,包括体内模型。
    Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1H)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1H)-one (benzoyl-)isothiocyanates, and the corresponding thioureide derivatives 8-11a-c were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC50 for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives 8,9a-c, in contrast to their acetyl-(benzoyl) derivatives and 10,11a-c, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9a has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC50 = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9c has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC50 = 12,94 mM). Compounds 8a, 8b, and 9b showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC50 against α-glucosidase for compounds 8a, 8b, and 9b was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds 8c, 10a, 10b, 10c, 11a, 11b, and 11c did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1H)-ones are promising candidates for the further modification and study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models.
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