含磷白杨素衍生物合成的研究进展

白杨素存在于许多水果和蔬菜中,具有多种生物活性,如抗癌、抗炎、抗氧化和抗突变等。但因其脂溶性和水溶性均较差,大大降低了其生物利用度,而引入含磷基团可有效地提高其脂溶性和水溶性,同时对其生物活性也有一定的提高。本文综述了含磷白杨素衍生物合成的研究进展。     

白杨素Mannich碱衍生物的合成及其抗癌活性

目的设计合成新型白杨素Mannich碱衍生物,并寻求具有抗癌活性的新化合物。方法利用Baker-Venkataraman重排法完成白杨素的全合成,再与甲醛、胺类进行Mannich缩合反应得到目标化合物。采用MTT法,以5-氟尿嘧啶为阳性对照,评价目标化合物对人宫颈癌细胞(Hela)、人肺腺癌细胞(A549)、人胃癌细胞(SGC-901)、人结肠癌细胞(HCT-116)、人白血病细胞(K562)5种肿瘤细胞的抗癌活性。结果与结论合成了10个未见文献报道的新化合物,其结构经1H-NMR、IR和MS确证。体外抗癌活性实验表明,部分化合物显示出较好的抗癌活性。     

白杨素抗肿瘤衍生物的合成及其构效关系

目的合成一系列白杨素衍生物并结合体外实验探讨白杨素衍生物抗肿瘤作用的构效关系。方法以5,7-二羟基黄酮为原料,通过取代、水解、酰胺缩合等化学反应引入一些极性不同的小分子化合物,合成一系列白杨素的衍生物,然后采用MTT比色法检测白杨素及其衍生物对食管癌EC109细胞、肝癌HepG2细胞、宫颈癌Hela细胞的增殖抑制作用。结果化合物Ⅲa、Ⅲb、Ⅲc、Ⅲd、Ⅲf对抑制EC109增殖表现出的抗癌活性较白杨素有明显的提高,化合物Ⅲa、Ⅲd、Ⅲe、Ⅲf对抑制HepG2增殖表现出的抗癌活性较白杨素有明显的提高,其中Ⅲd和Ⅲf的抗肿瘤作用显著;白杨素及其衍生物对抑制Hela细胞的增殖均较高,但其衍生物抗肿瘤作用与白杨素相比没有提高。结论引入极性基团对白杨素的抗肿瘤活性有明显的提高,经过极性基团修饰后的白杨素衍生物能明显提高对EC109、HepG2细胞增殖抑制作用。     

O^7-位硝酸酯类白杨素衍生物的合成及其促血管生成作用

白杨素在碳酸钾作用下,与二溴亚烷烃发牛亲核取代,再和硝酸银反应,使7-羟基与NO供体片段相连,得到3个新的O7-位硝酸酯类白杨素衍生物3a～3c,结构经.1HNMR、MS确证,并采崩鸡胚绒毛尿囊膜(CAM)技术初步考察了目标化合物的促血管生成作用.     

异丙酰基为桥合成白杨素氨基酸衍生物及其抗癌活性研究

目的　为改善天然产物白杨素的活性,利用氨基酸类物质特性,以异丙酰基为桥合成一系列白杨素氨基酸类衍生物,以期得到活性更高的衍生物。方法　采用烷基化、水解、酰胺缩合等药物合成方法在白杨素的7 位引入不同类型的氨基酸,得到一系列衍生物,运用1H-NMR 和13C-NMR 等方法对其结构进行确证;采用MTT 法,以白杨素母体、5-FU 为对照,检测其抗人肝癌细胞HepG2 和人乳腺癌细胞MCF-7 活性。结果　1H-NMR 和13C-NMR 等数据显示,烷酰基、氨基酸等基团被成功地引入到白杨素分子的7 位。活性测试结果显示,化合物2,5b,5d 抑制HepG2 细胞的IC50 值低于母体化合物白杨素,化合物2,3,4b,4c,4d,5a 和5c 抑制MCF-7 细胞的IC50 值低于白杨素。结论　通过实验能成功地将烷酰基、氨基酸等基团引入白杨素的7 位,且得到的大多数衍生物,相较于天然产物白杨素母体,具有更好的抗人肝癌细胞HepG2 和人乳腺癌细胞MCF-7 的活性。     

白杨素Mannich碱衍生物的合成及抗高尿酸血症活性

目的设计并合成新型具有抗高尿酸活性的白杨素Mannich碱衍生物。方法以天然产物白杨素为起始原料,与不同含氟有机物进行胺甲基化反应,合成系列白杨素Mannich碱衍生物。采用氯化硝基四氮唑蓝比色法测定目标化合物在体外对黄嘌呤氧化酶的抑制活性,并研究其在昆明种小鼠的体内抗高尿酸活性。结果与结论合成了10个未见文献报道的新化合物,目标化合物的结构经核磁共振氢谱和碳谱、电子轰击质谱(EI-MS)确证。体外活性实验显示,大多数含氟白杨素衍生物都具有较好的黄嘌呤氧化酶抑制作用,且体内抗高尿酸作用显著,在40 mg·kg~(-1)剂量时白杨素衍生物1a、1b、1c、1e、1f、1i和1j抗高尿酸效果最好,可使昆明种小鼠的血清尿酸值接近正常水平。     

7-羟乙基白杨素对PC12细胞的抗氧化作用及机制研究

目的 研究7-羟乙基白杨素对PC12细胞的抗氧化作用,并对其保护机制进行探讨。方法 使用CCK-8试剂盒检测PC12细胞的存活率,筛选出7-羟乙基白杨素作用的最佳浓度进行实验。之后将PC12细胞随机分为4组,分别为对照组、缺氧组、白杨素组和7-羟乙基白杨素组。使用微量酶标法测定细胞培养基中LDH活性,DCFH-DA染色观察细胞内ROS含量,同时使用试剂盒对细胞内MDA、SOD和CAT水平进行测定,提取细胞总蛋白通过Western blotting检测评价Nrf2及其下游蛋白表达量。结果 缺氧后PC12细胞存活率显著下降,经7-羟乙基白杨素预处理后可获得改善;白杨素组和7-羟乙基白杨素组上清液中的LDH和细胞内ROS、MDA含量与缺氧组相比显著降低,SOD和CAT含量与缺氧组相比显著升高,同时发现7-羟乙基白杨素在各个方面的保护作用都明显强于白杨素。缺氧条件会使Nrf2、Keap1、HO-1、NQO1蛋白表达增加,7-羟乙基白杨素干预后可以进一步提高它们的蛋白表达。结论 7-羟乙基白杨素具有比白杨素更好的保护效果,它可以通过激活Nrf2/ARE通路减轻PC12细胞由于缺氧造成的损伤。     

白杨素对大鼠矽肺纤维化的干预作用

目的 探讨白杨素对矽肺大鼠肺纤维化的干预作用。方法 SPF级雄性SD大鼠30只,随机分为5组：正常对照组、矽肺模型14 d组、矽肺模型56 d组、白杨素治疗14 d组和白杨素治疗56 d组。模型组大鼠予以气管灌注二氧化硅悬液(50 mg/只)造模,白杨素治疗组大鼠在造模后每天灌胃白杨素(50 mg·kg^-1)。采用肺功能仪对大鼠肺功能相关指标进行检测;HE染色观察大鼠肺组织的病理形态改变;天狼猩红染色观察大鼠肺组织中I、III型胶原的分布情况;试剂盒检测大鼠血清和肺泡灌洗液中转化生长因子-β1(transforming growth factor-β1,TGF-β1)的分泌水平,以及大鼠肺组织中的羟脯胺酸(hydroxyproline, HYP)的含量。结果 与对照组相比,矽肺模型14、56 d组大鼠肺部潮气量、每分钟通气量、呼吸频率均下降,气道狭窄指数均上升;肺组织中炎症细胞浸润均加重、矽结节数量均增多;Ⅰ、Ⅲ型胶原分布均增多;肺组织中HYP含量、肺泡灌洗液和血清中TGF-β1含量均升高。与模型组相比,白杨素治疗14、56 d组大鼠肺功能损害均减轻;肺组织中炎症...     

考察野黄芩素和白杨素的溶解度和稳定性

目的:考察野黄芩素和白杨素在纯水溶液中的溶解度以及在HBSS溶液中的稳定性,为药物的代谢研究和样品制备提供依据。方法:以药物在50%甲醇中的溶解度为标准,建立药物在纯水中的溶解度曲线,并考察药物在HBSS溶液中含量随时间变化的曲线,作为判断药物稳定性的依据。野黄芩素和白杨素的含量采用高效液相色谱法进行测定。结果:野黄芩素在0μM～102.4μM范围内可完全溶解,在7 d内0μM～25μM范围性质稳定。白杨素在0～25.6μm范围内可完全溶解,在2 d内0μM～25μM范围性质稳定,在7 d内0μM～12.5μM性质稳定。结论:野黄芩素和白杨素均在20μM的HBSS溶液溶解性和稳定性最好。     

蜂胶中白杨素和高良姜素的HPLC分析

目的:建立测定蜂胶中白杨素和高良姜素的反相高效液相色谱法,并用该方法测定9个产地蜂胶样品中白杨素和高良姜素的含量。方法:采用Zorbax SB-C_(18)(150mm×4.6mm,5μm)色谱柱;流动相:甲醇-0.1%甲酸;梯度洗脱:0→35min,甲醇-0.1%甲酸比例由(50∶50)→(75∶25);流速:1.0mL·min~(-1);检测波长:267nm;柱温:30℃。结果:白杨素在0.08～4.1μg(r=0.9999)范围内线性关系良好,其高、中、低3个量的平均加样回收率分别为99.1%,101.2%,99.7%;RSD分别为1.3%,1.8%,1.4%。高良姜素在0.06～3.8μg(r=0.9998)范围内线性关系良好,其高、中、低3个量的平均加样回收率分别为99.7%,100.6%,100.2%;RSD分别为1.0%,1.7%,1.8%。9个蜂胶样品中白杨素和高良姜素含量范围分别为2.25%～5.58%和2.18%～3.44%。结论:该方法是一种灵敏、准确的分析方法。     

Synthesis and cytotoxicity of novel chrysin derivatives

A series of chrysin derivatives 8a–8v were prepared and tested in vitro against HCT-116 (human colon cancer cell line), Hela (human cervical carcinoma cell line), DU-145 (human prostate cell line), K562 (human leukemia cell line), and SGC-7901 (human gastric cancer cell line). The chemical structures of these compounds were confirmed by means of MS, IR, ¹H NMR, ¹³C NMR, and elemental analysis. Among these derivatives, 7-(2-(piperazin-1-yl)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, 8n, had the strongest activity against HCT-116, Hela, DU-145, K562, and SGC-7901 cells. .     

Synthetic derivatives of chrysin and their biological activities

Chrysin is one of flavones constituents of Orocylumineicum vent. It has been a hot spot as a potential chemopreventive agent and as a natural molecule with numerous biological activities such as antioxidant, antitumor, antiviral, anti-hypertension, anti-diabetic, antibacterial, and so on in recent years. Because of its poor solubility, small intestinal absorption, and the rapid metabolism of glycosylation, a large number of efforts had been made by domestic and foreign researchers on designing its analogs and conjugates to obtain compounds with improved efficacy and selectivity for developing more active drugs for clinic. This article reviews the current research of studying on chrysin derivatives including their properties and possible applications. Additionally, this article also presents the basic information concerning chemical reactivity of chrysin, relevant to the synthesis of its derivatives.     

巴罗沙星与DNA的相互作用及Mg2+的影响

目的研究巴罗沙星与DNA的分子作用机制和Mg²⁺对巴罗沙星与DNA相互作用的影响。方法利用荧光光谱研究巴罗沙星与DNA的作用强度并计算热力学数据ΔH；利用紫外光谱、黏度测定、竞争实验、与变性DNA作用的比较等方法确定巴罗沙星与小牛胸腺DNA的相互作用方式；利用荧光光谱考察Mg²⁺对巴罗沙星与小牛胸腺DNA相互作用的影响。结果DNA对巴罗沙星的荧光猝灭常数为(5.43±0.07)×10³ L·mol^-1，ΔH=-8.03 kJ·mol^-1；Mg²⁺使巴罗沙星与DNA的作用增强。结论巴罗沙星以沟槽键合方式与DNA相互作用；Mg²⁺对巴罗沙星与DNA的结合有中介作用。     

DNA interaction,anti-proliferative effect of copper oxide nanocolloids prepared from metallosurfactant based microemulsions acting as precursor,template and reducing agent

In the present study, we have synthesized mixed cuprous/copper oxide nanosuspensions by metallosurfactant based microemulsion technique. Three metallosurfactants were synthesized which includes two non-ionic double chained metallosurfactants with C₁₂, C₁₆ chains with coordinated copper i.e. Cudda and Cuhexa, respectively. Another cationic double chained metallosurfactant with loosely bound metal (Cuctac) was also prepared. The prepared metallocomplexes were characterized using FTIR, elemental analysis, and NMR. The effect of the position of metallosurfactant in microemulsion on the fabrication and properties of nanosuspensions was elucidated. In this method, no external reducing agent and capping agent were added and tween 80 acted both as reducing and stabilizing agent for the nanoparticles. The synthesized nanoparticles were characterized and it was observed that mixed copper and cuprous oxide particles are present in colloidal suspension for all the three studied metallosurfactants. The kinetics of formation of mixed copper/cuprous oxide nanosuspensions (Ns) and their stability was estimated using Uv-visible spectroscopy. Further, the binding and interactions of copper nanosuspensions with calf Thymus DNA (CT-DNA) were assessed using Uv–vis spectroscopy, circular dichroism and gel electrophoresis. Additionally, the antioxidant activity of the Cu Ns was checked using DPPH assay. The role of positive charge on nanoparticles as evaluated from Zeta potential was responsible for DNA affinity. The DNA conformational changes in the presence of nanosuspensions and relevant scavengers were investigated. Further, the anti-proliferative activity of copper Ns was assessed using HeLa cells and Cuhexa derived Ns were proved to be active with highest activity at a low concentration and were nontoxic towards normal cell lines. In summary, this work demonstrates a softer approach for the synthesis of copper nanosuspensions with a size range of 2–5?nm and evaluated the role of type and structure of metallosurfactant on size, stability of particles and anti-proliferative activity.     

苯并噻唑希夫碱类化合物的合成及其与β-淀粉样蛋白结合性能的研究

阿尔茨海默病(Alzheimer’s disease,AD)是一种神经退行性疾病。随着人口老龄化,发病率逐年增高,不仅严重危害着老年人的健康,而且给家庭、社会带来了巨大的经济和人力负担。在我国1.3亿老年人中,痴呆患者600～700万人,发病率在5%以上,约占世界总病例的1/4,成为世界老年痴呆症第一大国[1]。AD常隐匿起病,逐渐出现记忆力减退、认知