姜黄素及其类似物诱导人早幼粒白血病(HL-60)细胞调亡

姜黄素(Curcumin,Cur)是烹饪调味品姜黄中的一种黄色色素,具有抗癌、抗炎、抗氧化等多种药理作用[1～3].为了研究它的抗肿瘤构效关系,我们合成了一系列姜黄素类似物(结构见Scheme 1),研究了它们诱导HL-60细胞凋亡的活性及构效关系.采用MTT法测定细胞存活率,通过细胞形态学、DNA电泳梯形条带、流式细胞仪来观察及检测细胞的凋亡.结果发现姜黄素及其类似物作用48 h后能抑制HL-60细胞增值,诱导HL-60细胞凋亡.其中Cur,DMCur,MCur,DiMCur和DiACCur的作用较强.     

姜黄素及其类似物对自由基诱导的线粒体过氧化的保护作用

姜黄素(curcumin,1)是烹饪调味品姜黄中的一种黄色色素,具有抗炎、抗氧化、免疫调节、抗癌、抗高血脂等多种药理作用[1-3].为了研究它的抗氧化活性构效关系,我们合成了一系列姜黄素类似物,研究了它们对自由基诱导的大鼠肝脏线粒体过氧化的保护作用.分别采用水溶性的偶氮引发剂2,2'-偶氮二(2-脒基丙烷)二盐酸盐(AAPH)热分解产生过氧自由基(ROO·)及Fenton反应产生羟自由基(HO·)引发大鼠线粒体的过氧化,通过检测硫代巴比妥酸反应物质(TBARS)的含量测量过氧化的程度,结果发现姜黄素及其类似物均能够不同程度地抑制线粒体的过氧化.其中Curcumin,DMC和MC的抗氧化作用较强(Figure 1).     

姜黄素及其类似物对自由基诱导的红细胞溶血的抑制作用

自由基诱导的细胞膜脂质过氧化和DNA氧化性损伤被认为与癌症、动脉硬化等疾病有关[1].姜黄素(1)是烹饪调味品中的一种黄色色素,具有抗癌、抗炎、抗氧化等多种药理作用[2].我们合成了一系列姜黄素及其类似物1～7,以自由基诱导的红细胞溶血为模型,研究了它们的抗氧化活性.发现这些化合物对以水溶性自由基引发剂AAPH诱导的红细胞溶血都有抑制作用(Figure 1),并且具有邻位酚羟基的化合物3和4比姜黄素和其他类似物具有更高的活性.这为抗氧化治疗药物的发展提供了有用的信息.     

姜黄素的构效关系及以其为先导物的抗肿瘤化合物研究进展

姜黄素具有抗肿瘤、抗炎、抗菌、抗氧化等多种药理作用和确切疗效.近年来国内外科学家以姜黄素为先导物,设计、合成和表征了大量的姜黄素结构类似物和衍生物,以全面研究姜黄素的构效关系,并希望开发出更为高效的姜黄素类新药物.本文着重于介绍近年在抗肿瘤作用上针对姜黄素构效关系及其结构类似物进行的研究工作.     

超声辅助法研究姜黄素对牛血清白蛋白损伤的影响

运用荧光法研究了姜黄素对牛血清白蛋白(BSA)的荧光猝灭机理,并结合紫外可见光谱探讨了超声照射下姜黄素对BSA的损伤。结果表明,姜黄素对BSA的荧光属静态猝灭,超声作用对牛血清白蛋白的分子结构影响较小,促进了姜黄素对牛血清白蛋白内源荧光的猝灭作用,使猝灭常数增大,辅助姜黄素进一步损伤蛋白质。原因可能是超声波激活姜黄素产生活性物质,活性物质氧化BSA分子内的氨基酸残基,破坏BSA分子结构。姜黄素对牛血清白蛋白的损伤程度随照射时间(0～5h)和姜黄素浓度(0～2.5×10-5mol·L-1)的增大而增加。研究结果为姜黄素作为一种天然光敏剂用于声动力学(SDT)提供了指导意义。     

姜黄素衍生物与类似物的构效关系研究进展

根据目前对姜黄素衍生物与类似物的结构与药理作用的关系的研究现状,论述了姜黄素衍生物与类似物的结构与其抗氧化、抗炎和抗肿瘤的药理作用的关系,包括对姜黄素及其衍生物与类似物的结构修饰与其活性之间的关系的论述。大量的实验结果显示姜黄素衍生物与类似物的药理作用与其结构中所具有的官能团有着密切的关系,这为新药开发提供了一个很好的方向。     

姜黄素-4-肟的合成及与牛血清白蛋白相互作用的荧光光谱研究

本文通过先导物姜黄素合成了4-肟基-(E,E)-1,7-双(4-羟基-3-甲氧基苯基)-1,6-庚二烯-3,5-二酮(姜黄素-4-肟)。通过IR、1H NMR、13C NMR及ESI-MS对产物结构进行了表征。用荧光光谱法研究了姜黄素-4-肟与牛血清白蛋白(BSA)之间的相互作用。结果表明:姜黄素-4-肟对BSA有较强的荧光猝灭作用,且为静态猝灭。实验分别获得了姜黄素-4-肟在不同温度与BSA作用的猝灭常数Ksv、猝灭速率常数kq及热力学参数。姜黄素-4-肟和BSA之间是以疏水作用力为主。     

高效液相色谱/化学发光法测定盐酸青藤碱

盐酸青藤碱(sinomenine hydrochloride,SIN,青藤碱的结构式见图1。)是从植物青风藤(Sinom eniumsctumRehd.etW ils)中提取生物碱单体盐酸盐。具有抗炎、免疫抑制、镇痛、降压、抗心率失常等药理作用,临床用于治疗类风湿性关节炎等各种风湿病以及心率失常,取得较好疗效[1]。已报     

姜黄素联合顺铂对卵巢癌细胞COC1的体外抗肿瘤作用

利用MTT比色法研究了姜黄素(Cur)联合顺铂（DDP）对卵巢癌COC1细胞的抑制作用。 结果表明,当ρ(DDP)为2.5~10 mg/L,ρ(Cur)=5 mg/L时,与DDP相比,二者联合用药对卵巢癌COC1细胞可产生协同抑制作用;ρ(Cur)=5 mg/L就可明显增强COC1细胞对顺铂的敏感性,增敏倍数为2.66倍;光学显微镜观察发现,药物作用后COC1细胞的形态发生了改变,细胞折光度下降,大小不一、形态各异、排列疏散和胞浆空泡化严重。 为探讨姜黄素协同顺铂抑制肿瘤的机制,本研究采用高效液相色谱法测定姜黄素辅助用药前后细胞内DDP含量的变化。 结果表明,在加入姜黄素前后,COC1细胞内顺铂含量虽然略有下降,但差异无统计学意义（P＞0.05）。 由此可见,姜黄素与顺铂联合用药对人卵巢癌COC1细胞增殖具有协同抑制作用,且姜黄素可同时增加COC1细胞对顺铂的敏感性,但姜黄素可能并未明显改变顺铂在细胞内的含量,即姜黄素可能不是通过影响顺铂进入细胞的通路而起协同抑制作用的。     

荧光光谱法研究姜黄素与β-环糊精及其衍生物包合作用

采用荧光光谱法,在室温下研究了pH=2.02的磷酸盐缓冲溶液中β-环糊精(β-CD)、甲基-β-环糊精(M-β-CD)、羟丙基-β-环糊精(HP-β-CD)、磺丁基-β-环糊精(SBE-β-CD)对姜黄素的包合作用。固定姜黄素浓度,逐渐改变β-CD及其衍生物的浓度,姜黄素的荧光强度逐渐增强,表明包合物的形成,同时用荧光双倒数法计算了β-CD及其衍生物与姜黄素的包合常数。结果表明,室温下,在pH=2.02的磷酸盐缓冲体系中,SBE-β-CD对姜黄素的包合能力最强,四种环糊精与姜黄素的包合比均为1∶1。初步探讨了SBE-β-CD荧光增敏作用对姜黄素的定量测定,线性范围为5.0×10-7～4.5×10-6 mol/L,检出限为1.2×10-8 mol/L。     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.