糖基化三氮唑香草酸白杨素酯的合成与结构表征

以叠氮糖、炔丙基溴、香草醛和白杨素为原料,通过醚化、"Click chemistry"氧化、酯化4步反应得到4个糖基化三氮唑香草酸白杨素酯,反应路线简单,条件温和,收率较高,总收率为51%~62%(以香草醛计),产物结构通过1H NMR、IR、ESI-MS和元素分析确认。     

糖基化三氮唑鹰嘴豆芽素A衍生物的合成与抗缺氧活性研究

以叠氮糖、炔丙基溴和鹰嘴豆芽素A为原料,利用"Click chemistry"将糖基化三氮唑药效基团与鹰嘴豆芽素A巧妙结合,得到4种新的标题化合物,产物结构经1HNMR、13CNMR、IR、EI-MS和元素分析确认。通过小鼠常压密闭耐缺氧模型对其药理活性进行评价,结果表明:4个目标化合物均不同程度地延长小鼠的存活时间,其中半乳糖苷三氮唑鹰嘴豆芽素A和木糖苷三氮唑鹰嘴豆芽素A的活性优于乙酰唑胺。     

基于巯基三氮唑及其衍生物构筑配合物的研究进展

巯基三氮唑是一种含硫氮杂环有机化合物,由于具有多个配位点和较强的配位能力以及衍生物的多样性, 近些年在配位化合物、医药等方面受到广泛研究。本文按照取代基数目的不同将巯基三氮唑衍生物分为疏基三 氮唑、单取代巯基三氮唑、多取代巯基三氮唑、多臂巯基三氮唑衍生物,并按照分类系统地总结了近些年来这 类配体及其金属配合物的合成方法和结构特征方面的研究成果,同时介绍了其金属配合物在药物、功能材料方 面的应用。最后依据巯基三氮唑及其衍生物构筑配合物的研究现状,从配体、金属离子两方面对巯基三氮唑未 来的研究方向进行了展望。     

白杨素糖苷类衍生物的合成及其结构表征

以白杨素为前体,针对白杨素的溶解性进行改进,在白杨素7位羟基处引入糖单元,合成12种白杨素糖苷类衍生物,步骤简单,条件温和,收率较好。利用1HNMR、13CNMR和MS等方法确定了所合成化合物的结构。     

1,2,4-三氮唑并[1,5-α]嘧啶类衍生物的研究进展

本文概述了三氮唑并嘧啶磺酰胺、三氮唑并嘧啶硫代乙酰芳胺和三氮唑并嘧啶硫醚等三个系列的三氮唑并嘧啶类衍生物的国内外最新研究进展。     

白杨素衍生物的合成及其活性研究

合成白杨素衍生物并对其进行活性评价。以5,7-二羟基黄酮为原料,通过取代、水解、酰胺缩合反应合成白杨素的衍生物,然后采用MTT比色法测定白杨素及白杨素衍生物对EC109（食管癌）、HepG2（肝癌）、SW480（结肠癌）、Hela（宫颈癌）细胞增殖抑制作用。合成的白杨素衍生物对HepG2、SW480肿瘤细胞的IC50值比白杨素的IC50值低。该衍生物对HepG2、SW480肿瘤细胞的抗癌活性较白杨素有一定程度的提高。     

苯并三氮唑乙酸乙酯的合成、热稳定性及几何空间结构优化研究

以苯并三氮唑为起始原料,经与氯乙酸反应制备得到苯并三氮唑乙酸,再与乙醇进行酯化反应合成得到苯并三氮唑乙酸乙酯。对产物苯并三氮唑乙酸乙酯的热稳定性研究显示苯并三氮唑乙酸乙酯在230℃后开始分解,具有良好的热稳定性;而升温速率对苯并三氮唑乙酸乙酯的起始分解温度会产生较大的影响。同时借助密度泛函对产物进行了结构优化。结果表明,苯并三氮唑乙酸乙酯分子电子密度分布较为均匀,优化后苯并三氮唑乙酸乙酯的HOMO和LUMO值分别为-0.213 528 e V和-0.072 481 e V。     

苯并三氮唑乙酸乙酯的合成、热稳定性及几何空间结构优化研究

以苯并三氮唑为起始原料,经与氯乙酸反应制备得到苯并三氮唑乙酸,再与乙醇进行酯化反应合成得到苯并三氮唑乙酸乙酯。对产物苯并三氮唑乙酸乙酯的热稳定性研究显示苯并三氮唑乙酸乙酯在230℃后开始分解,具有良好的热稳定性;而升温速率对苯并三氮唑乙酸乙酯的起始分解温度会产生较大的影响。同时借助密度泛函对产物进行了结构优化。结果表明,苯并三氮唑乙酸乙酯分子电子密度分布较为均匀,优化后苯并三氮唑乙酸乙酯的HOMO和LUMO值分别为-0.213 528 e V和-0.072 481 e V。     

线粒体靶向白杨素的设计、合成与抗缺氧活性研究

为了提高天然产物白杨素的生物活性,以长链烷基为桥联基,通过2步反应将白杨素与线粒体靶向配体三苯基膦偶联得到了3个线粒体靶向白杨素衍生物。目标化合物分子结构经红外光谱(IR)、核磁共振谱(~1H NMR和~(13)C NMR)和质谱(MS)分析确证。常压密闭缺氧实验结果表明:3个衍生物均能延长缺氧小鼠的存活时间,且活性显著优于白杨素。     

合成1-(4-苯基-1,2,3-三氮唑-1-亚甲基)苯并三氮唑的新方法

三氮唑类衍生物具有抗菌、抗炎、抑制病毒生长等广泛的生物活性。从苯并三氮唑出发,通过点击化学反应在水相中合成了1-(4-苯基-1,2,3-三氮唑-1-亚甲基)苯并三氮唑,产率为91%;该合成方法具有简便快速、产率高等优点。     

Apoptotic Effects of Chrysin in Human Cancer Cell Lines

Chrysin is a natural flavonoid currently under investigation due to its important biological anti-cancer properties. In most of the cancer cells tested, chrysin has shown to inhibit proliferation and induce apoptosis, and is more potent than other tested flavonoids in leukemia cells, where chrysin is likely to act via activation of caspases and inactivation of Akt signaling in the cells. Moreover, structure-activity relationships have revealed that the chemical structure of chrysin meets the key structural requirements of flavonoids for potent cytotoxicity in leukemia cells. It is possible that combination therapy or modified chrysin could be more potent than single-agent use or administration of unmodified chrysin. This study may help to develop ways of improving the effectiveness of chrysin in the treatment of leukemia and other human cancers in vitro.     

Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial–Mesenchymal Transition

Cyclosporine A (CsA) is a nephrotoxicant that causes fibrosis via induction of epithelial–mesenchymal transition (EMT). The flavonoid chrysin has been reported to have anti-fibrotic activity and inhibit signaling pathways that are activated during EMT. This study investigated the nephroprotective role of chrysin in the prevention of CsA-induced renal fibrosis and elucidated a mechanism of inhibition against CsA-induced EMT in proximal tubule cells. Treatment with chrysin prevented CsA-induced renal dysfunction in Sprague Dawley rats measured by blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Chrysin inhibited CsA-induced tubulointerstitial fibrosis, characterized by reduced tubular damage and collagen deposition. In vitro, chrysin significantly inhibited EMT in LLC-PK₁ cells, evidenced by inhibition of cell migration, decreased collagen expression, reduced presence of mesenchymal markers and elevated epithelial junction proteins. Furthermore, chrysin co-treatment diminished CsA-induced TGF-β₁ signaling pathways, decreasing Smad 3 phosphorylation which lead to a subsequent reduction in Snail expression. Chrysin also inhibited activation of the Akt/ GSK-3β pathway. Inhibition of both pathways diminished the cytosolic accumulation of β-catenin, a known trigger for EMT. In conclusion, flavonoids such as chrysin offer protection against CsA-induced renal dysfunction and interstitial fibrosis. Chrysin was shown to inhibit CsA-induced TGF-β₁-dependent EMT in proximal tubule cells by modulation of Smad-dependent and independent signaling pathways.     

Chrysin Protects against Focal Cerebral Ischemia/Reperfusion Injury in Mice through Attenuation of Oxidative Stress and Inflammation

Inflammation and oxidative stress play an important part in the pathogenesis of focal cerebral ischemia/reperfusion (I/R) injury, resulting in neuronal death. The signaling pathways involved and the underlying mechanisms of these events are not fully understood. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. In this study, we investigated the neuroprotective properties of chrysin in a mouse model of middle cerebral artery occlusion (MCAO). To this end, male C57/BL6 mice were pretreated with chrysin once a day for seven days and were then subjected to 1 h of middle cerebral artery occlusion followed by reperfusion for 24 h. Our data show that chrysin successfully decreased neurological deficit scores and infarct volumes, compared with the vehicle group. The increases in glial cell numbers and proinflammatory cytokine secretion usually caused by ischemia/reperfusion were significantly ameliorated by chrysin pretreatment. Moreover, chrysin also inhibited the MCAO-induced up-regulation of nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the vehicle. These results suggest that chrysin could be a potential prophylactic agent for cerebral ischemia/reperfusion (I/R) injury mediated by its anti-inflammatory and anti-oxidative effects.     

Chrysin,Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1) on Activated RAW264.7 Macrophages

Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4'' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.     

白杨素分子印迹聚合物的制备及其性能评价

以白杨素为模板分子,硅胶为载体,丙烯酰胺为功能单体,采用表面印迹法制备白杨素分子印迹聚合物。并通过红外光谱测定,吸附实验等对印迹聚合物进行表征及性能评价。静态吸附实验表明,印迹聚合物对模板分子的吸附量远远高于非印迹聚合物;印迹聚合物及非印迹聚合物对白杨素、氯霉素、甲砜霉素的选择吸附表明,所制备的分子印迹聚合物对白杨素有特异性吸附效果。     

Physicochemical Characterization of Chrysin‐Derivative‐Loaded Nanostructured Lipid Carriers with Special Reference to Anticancer Activity

Homologues long‐chain chrysin derivatives (LCD, C _n: 8–18) were synthesized and incorporated into nanostructured lipid carriers (NLC) with the aim to treat human neuroblastoma. Mutual miscibility and attractive interactions among the NLC components, namely tripalmitin (TP), cetyl palmitate (CP), oleic acid (OA), and the chrysin (CHR) derivatives (LCD) at the air–water interface were assessed by the Langmuir monolayer approach. Optimum combination for the NLC formulations was found to be 2:2:1 (M/M/M) for TP/CP/OA, respectively. NLC formulations, both in the absence and presence of LCD, were characterized by combined dynamic light scattering, electron microscopy, atomic force microscopy, and differential scanning calorimetry. The size and zeta potential of the NLC formulations were found in the range 200–350 nm and ?12 to ?18 mV, respectively. Encapsulation efficiency and release kinetics of CHR and LCD when loaded into NLC were also evaluated. LCD exhibited maximum incorporation, drug‐loading capacity, and sustained release because of its enhanced hydrophobicity. Superior incorporation efficiency and sustained‐release profile of LCD were able to enhance their anticancer activity against human neuroblastoma cell lines, compared to CHR, making them promising agents in combating cancer.     

The potential of flavonoids as natural antioxidants and UV light stabilizers for polypropylene

This article presents a study on the stabilization of polypropylene against thermo‐oxidation and UV radiation by using natural phenolic compounds derived from the structures of flavonoids: a flavone (chrysin), a flavanol (quercetin), two flavanone glycosides (hesperidin and naringin), and flavanoligand (silibinin). Thermal stabilization has been assessed in an oxidizing atmosphere by means of differential scanning calorimetry both in isothermal and in dynamic conditions. In addition, the effectiveness of these phenolic compounds as thermal stabilizers at high temperature has been quantified with the use of thermogravimetric analysis. Stabilization against UV radiation has been estimated by studying the morphology changes of the exposed surfaces by scanning electron microscope (SEM); also, surface chemical changes have been followed by infrared spectroscopy. Global results show that flavonoid compounds of type flavonols (quercetin and silibinin) provide the best results in stabilizing both against oxidation and against the action of UV radiation. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013