姜黄素类似物的合成及其清除自由基的研究

姜黄素(见图1)为中药姜黄的主要成分,是一种黄色色素。研究报道姜黄素具有抗氧化、抗炎、抗病毒、抗癌等生物活性[1-4]。本文通过芳香醛和环己酮催化缩合反应合成了一系列姜黄素类似物(见图2),研究了它们抗自由基的活性。图1姜黄素的化学结构F ig.1 Chem ical structure of cur     

不对称姜黄素类似物的合成及其清除自由基的研究

姜黄素类化合物中,非对称结构的单去甲氧基姜黄素具有一些特殊的生物活性.通过碱法合成2-单取代苯亚甲基环戊酮中间体,再用酸催化合成了10不对称的单羰基姜黄素类似物,多酚羟基的类似物可以不通过羟基保护直接合成,其中,除A1外其它9个为新化合物,并测试了所合成类似物对DPPH自由基的清除能力.结果表明类似物的酚羟基对自由基清...     

新型姜黄素类似物的微波合成及其抗氧化活性

采用微波法,取代苯甲醛分别与环戊酮和环己酮经克莱森-斯密特缩合反应制得中间体2,6-双苯亚甲基环己酮(2a~2e)和2,5-双苯亚甲基环戊酮(5a);2a~2e或5a分别与硫脲或尿素经Biginelli反应合成了8个新型的姜黄素类似物(3a~3e,4a,4c和6a),其结构经1H NMR,13C NMR,IR和MS表征。利用DPPH法比较3~6与姜黄素的抗氧化能力。实验结果表明:3~6的抗氧化能力均比姜黄素母核结构高;3比4和6的自由基清除能力强;随用药量增大,抗氧化能力呈现先增强后下降的趋势,并在0.09 mg·mL-1~0.12 mg·mL-1自由基清除率达最大。     

新型含氟姜黄素类似物的合成、晶体结构及抗肿瘤活性

采用活性基团拼接法将含氟苯甲醛与酮反应, 合成了5个含氟单羰基姜黄素类似物, 结构经IR, ¹H NMR及ESI-MS确认. 对所合成的化合物进行了抗肿瘤活性测试(MTT法), 结果表明, 部分化合物对肿瘤细胞有较强的选择性抑制活性, 其中2,6-二(4-氟亚苯基)环己酮(3a)和2,6-二(2-氟亚苯基)环己酮(3b)的抗肿瘤谱广, 活性较好, 就此对化合物3b作了单晶培养, 并就晶体结构进行了X衍射分析. 结构表明化合物3b属三斜晶系, 空间群 P-1. 晶胞参数 a＝0.9222(2) nm, b＝0.9732(2) nm, c＝1.0127(2) nm, α＝88.920(4)°, β＝75.672(3)°, γ＝62.404(3)°, V＝0.7755(3) nm³, Z＝2, D_c＝1.329 Mg•m^－3, μ＝0.097 mm^－1, F(000)＝324, 最终偏离因子R＝0.0590, wR＝0.1841.     

含哌啶酮结构单元的姜黄素类似物的合成及其诱导癌细胞凋亡活性

以邻甲氧基苯甲醛为原料,经羟醛缩合反应合成了6个单羰基姜黄素类似物（1a~1f）,其结构经¹H NMR和¹³C NMR确证。采用MTT法研究了1a~1f对人肺癌细胞A549和NCI-H460的抑制活性。结果表明：大部分化合物的活性显著优于天然产物姜黄素。其中3,5-二(2-甲氧基苯亚甲基)-4-哌啶酮（1d）可促进细胞活性氧的产生,对A549有诱导凋亡效果。     

螺杂环单羰基姜黄素类似物的合成、晶体结构与抗肿瘤活性研究

为了发现新型姜黄素类抗肿瘤先导化合物,通过1,3-偶极环加成反应合成了14个螺杂环单羰基姜黄素类似物.该反应利用无需加催化剂的"一锅煮"方法合成,具有环境友好的优点.所有化合物结构经ESI-MS、ESI-HRMS和1H NMR确认,通过X衍射确证B6的晶体结构为单斜晶系,该类化合物的合成具有良好的区域选择性和立体选择性.通过噻唑兰(MTT)法测定所有化合物对人胃癌细胞SGC-7901、神经胶质瘤细胞U251、人大细胞肺癌细胞株NCI-H460的增殖抑制活性,部分化合物表现出了较好的活性.其中B1、B6、B7和B11对三种肿瘤细胞均表现出较好的抗肿瘤活性,而对正常人肝细胞HL-7702显示了相对较低的细胞毒性.化合物B1和B7均能明显诱导凋亡相关蛋白含半胱氨酸的天冬氨酸蛋白水解酶3(caspase3)和多聚ADP-核糖聚合酶(PARP)的活化,诱导肿瘤细胞发生凋亡.所合成的螺杂环单羰基姜黄素类似物为新型的抗肿瘤化合物,该类化合物可能在靶向抗肿瘤药物研发方面具有较好的研究前景.     

含氮含硫姜黄素类似物的微波合成及抗氧化活性研究

利用微波辐射合成含氮含硫的姜黄素类似物,比较了化合物的抗氧化能力。以苯甲醛与环戊酮或环己酮为原料,经克莱森-斯密特缩合反应,采用微波法合成中间化合物2,6-双苯亚甲基环己酮或2,5-双苯亚甲基环戊酮,中间体与尿素或硫脲经Biginelli反应合成目标化合物。利用DPPH法比较各化合物与姜黄素的抗氧化能力。合成了2个未见文献报道的新化合物(2b,2c),结构经IR、1H NMR、13C NMR和MS表征确证;增加含氮、含硫基团的衍生物,其抗氧化能力比姜黄素母核结构高。采用微波法合成含氮含硫的姜黄素类似物可显著提高产率,产率达83%,经24 h含氮、含硫化合物b的抗氧化能力与姜黄素相当,远比姜黄素母核强。     

姜黄素类似物合成与抗抑郁活性研究

<正>世界卫生组织(WHO)提出:抑郁是世界第四大健康问题,到2020年,抑郁将成为第二大健康负担[1,2]。尽管在三环类抗抑郁药和单胺氧化酶抑制剂(MAOIs)之后又陆续出现了新的抗抑郁药如:选择性5-HT再摄取抑制剂(SSRI,氟西汀);     

多酚姜黄素类似物的一步合成

以无水乙醇或THF为溶剂,浓盐酸为催化剂,含羟基芳香醛可以在不保护酚羟基的情况下与酮一步完成缩合反应,合成了12个多酚姜黄素类似物,产率62%～98%,其结构经1H NMR,MS,IR和元素分析确证.     

新型双环新烟碱类似物的合成及其生物活性

设计合成了六个新型双环新烟碱类似物,通过1H NMR,13C NMR,高分辨质谱和单晶结构对目标化合物的结构进行了表征.初步的生物活性测试表明:在500 mg?L-1浓度下,目标化合物6a,6c~6f对豆蚜(Aphis craccivora)具有很好的杀虫活性.通过分子对接比较并解释了目标化合物6a和吡虫啉的活性和作用模式的差异,其结果表明目标化合物6a的吡啶环和受体残基色氨酸147的芳香环侧链具有?-?堆积作用,与吡虫啉的作用方式存在一定差异.     

Synthesis and evaluation of pyrazole‐incorporated monocarbonyl curcumin analogues as antiproliferative and antioxidant agents

A series of pyrazole‐incorporated monocarbonyl analogues of curcumin were synthesized via Clasien–Schimidt‐type condensation and subsequently screened for in vitro antiproliferative and antioxidant activity. The analogues 4c, 5d, 5e, 5g, 6e, and 6f showed potential activity against the MDA‐MB‐231 cell line. The synthesized analogues were also screened for their antioxidant activity. Compounds 5a , 5e , 6d, and 6f exhibit comparable radical scavenging activity with respect to the standard drug ascorbic acid. Furthermore, a molecular docking study has been conducted for 5d and 5g and suggests that these compounds have a potential to become lead molecules in drug discovery and process.     

Synthesis and cytotoxic activity of novel curcumin analogues

Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.     

Synthesis of Asymmetric Curcumin Analogues from CullilawanOil using Conventional and Microwave Method

Asymmetric curcumin analogues as potential anticancer compounds. The purpose of this study was to synthesize product 5-benzo[1,3]dioxol-5-yl-1-phenyl-penta-2,4-dien-1-one uses the method conventional and microwaves. Product 5-benzo[1,3]dioxol-5-yl-1-phenyl-penta-2,4-dien-1-one can be synthesized from the cullilawan oils with several stages, among others; isolation safrole, isomerization, oxidation and condensation reactions. Isolation of safrole from cullilawanoils performed using NaOH solution and purified using distillation fractionation pressure reduction produces 19.30% safrole are tested for purity by GCMS and for the identification of the structure is done by using FTIR and ¹H-NMR. The safrole isomerization performed using KOH without solvent at a temperature of 120^oC for 8 hours resulted isosafrole (91.53%) which consists of cis-isosafrol and trans-isosafrol. Oxidation isosafrole performed using KMnO₄ in acidic conditions using a phase transfer catalyst tween 80 at a temperature of < 30^oC and separation by silica gel resulted in 65.63% piperonal were tested with the GCMS and identification using FTIR and ¹H-NMR. Products asymmetrical curcumin analogous made in the condition alkaline by conventional methods for three hours produce 99.55%, a method of microwaves in 140 watts for two minutes produce 82.82%.     

Liquid crystalline analogues of curcumin

Compounds that are modifications of curcumin were synthesised and their mesogenic properties were studied. The central keto-enolic ring in curcumin was replaced by either a pyrazole or an isoxazole ring. This gives compounds that can form liquid crystalline phases. When two alkoxy chains are attached to the molecule, nematic and lamellar phases appear; in the case of six alkoxy chains, a hexagonal columnar phase is created. The columnar phase is constructed from columns that in the cross-section have two molecules. The pyrazole derivatives in the columnar phase preserve N–H–N hydrogen bonding.     

Synthesis,characterization, and polymerization of propenyl ether analogues

A series of aromatic monomers bearing cationically polymerizable propenyl groups were prepared and characterized using the readily available starting materials: isoeugenol and o-allyl phenol. Monomers with both propenyl and vinyl ether functional groups were also synthesized by the reaction of these starting materials with chloroethyl vinyl ether. The reactivity of the resulting monomers in photoinitiated cationic polymerization was studied using differential scanning photocalorimetry and photogel point measurements. Their thermal properties were determined using thermogravimetric analysis. © 1994 John Wiley & Sons, Inc.     

Synthesis of N-1 and ribose modified inosine analogues on solid support

Herein, we report the synthesis and the use of new N-1-dinitrophenyl-inosine based solid supports, in which the C-2 of the purine base is strongly activated toward the attack of N-nucleophiles. The synthesized supports, binding the nucleoside by a 5′-O-monomethoxytrityl function, have been used to accomplish the synthesis of a small library of N-1 alkylated inosine and AICAR derivatives. In addition, cleavage of the 2′-3′ ribose bond of N-1 alkylated inosine derivatives anchored to the supports allowed to prepare a new set of N-1 alkylated-2′,3′-secoinosine derivatives in high yields.     

Adsorptive transfer voltammetry applied to the study of chromium-induced DNA damage in the presence of curcumin

The interaction between double-stranded (ds) calf-thymus DNA and chromium in the presence of curcumin (CC) was studied by differential pulse adsorptive transfer voltammetry using carbon paste electrode (CPE). Curcumin–Cr complex generated changes in calf thymus DNA. The mechanism for DNA cleavage by curcumin–Cr complex appears to involve both the hydroxyl radical as well as singlet oxygen. The characteristic peak of dsDNA, due to the oxidation of guanine residues, drastically decreased. The increased DNA damage by curcumin–Cr complex was observed in the presence of various concentrations of chromium(VI).     

3-羟基-4-氨基丁酸及其类似物的合成进展

3-羟基-4-氨基丁酸（简称GABOB）是一类有趣的氨基酸，它的一些类似物如Statine等存在于一些具有抗肿瘤、抗病毒、抗炎症等生理活性的天然产物之中。从治疗的角度讲，3-羟基-4-氨基丁酸也具有重要意义。本文简要介绍GABOB类似物的天然存在及生理活性，并从不同的起始原料出发介绍它们的立体选择性合成。