新型砜基喹喔啉衍生物的合成和体外抗肿瘤活性研究

合成了新型的砜基喹喔啉衍生物并对其体外抗肿瘤活性进行初步评价。采用Kinase-Glo Luminescent Assay,Lance Ultra Assay,SRB法测试砜基喹喔啉类衍生物的体外抗肿瘤活性。9个砜基喹喔啉衍生物经NMR,MS表征;砜基喹喔啉衍生物对PI3Kα、哺乳动物雷帕霉素靶蛋白(mTOR)均无明显的抑制作用;其中,化合物3-(3-氨基苯磺酰基)-N-(3,5-二甲氧基苯基)喹喔啉-2-胺(12),N-(3-(3-(3,5-二甲氧基苯胺基)喹喔啉-2-基砜基)苯基)乙酰胺(13)、1-(3-(3-(3,5-二甲氧基苯胺基)喹喔啉-2-基砜基)苯基)-3-乙基脲(15)和N-(3-(3-(3,5-二甲氧基苯胺基)喹喔啉-2-基砜基)苯基)吗啉-4-甲酰胺(16)对PC3细胞的增殖抑制活性(IC₅₀)均<3μmol/L。砜基喹喔啉类衍生物具有中等强度的抗肿瘤活性。     

建设项目动态

1　 2 -羟基喹喔啉2 -羟基喹喔啉是重要的农药、医药中间体。 2 -羟基喹喔啉与乙基氯化物反应生产杀虫剂喹硫磷 ,用于防治粮食、棉花和果蔬等经济作物的刺吸式和咀嚼式口器害虫、钻蛀性害虫和螨类。 2 -羟基喹喔啉氯化得到 6-氯 - 2 -羟基喹喔啉 ,用于生产除草剂喹禾灵 ,其除草活性高 ,对一年生或多年生禾本科杂草在任何生长期均有效。 2 -羟基喹喔啉与三氯氧磷反应得到 2 -氯喹喔啉 ,用于生产兽药磺胺喹喔啉 ,可预防和治疗球虫病 ,促进畜禽生长。 2 -羟基喹喔啉还用于抗癌新药生产 ,此外 ,利用其弱碱性还作为半导体刻蚀添加剂。目前 ,国内 …     

3-氯-2,6-二硝基喹喔啉的合成工艺研究

喹喔啉为一类重要的苯并吡嗪类杂环化合物,喹喔啉衍生物在医药及化工合成领域具有重要的作用.3-氯-2,6-二硝基喹喔啉是一种重要医药化工中间体.本文以2-羟基喹喔啉为原料,经硝化反应和氯代反应两步反应得到目标化合物.该合成方法操作简便、后处理操作简便,花费时间少且产物纯度高、收率也较高,产品收率为58.2％,适合工业化生...     

2-异丙基喹喔啉衍生物的合成及应用

以邻苯二胺化合物和α-溴代酮类化合物为原料,经过串联环化反应合成喹喔啉类化合物。部分未知的喹喔啉衍生物经过质谱和核磁分析加以确证。同时研究了2-异丙基喹喔啉在过渡金属Ag参与下的sp3C—H键硝化反应。     

1,4-二氧喹喔啉甲醛双腙的合成及除草活性研究

用1,4-二氧-2-喹喔啉甲醛、水杨醛、甲醛、乙醛、丙酮、丁烯醛、环戊酮和环己酮与水合肼反应制备了8种中间体单腙,再用这些单腙与1,4-二氧-2-喹喔啉甲醛反应合成了8种双腙新化合物,并进行了表征。对这些新化合物对油菜和稗草进行了除草活性研究。研究结果表明1,4-二氧喹喔啉-2-甲醛-水杨醛双腙和1,4-二氧喹喔啉-2-甲醛-丙酮双腙表现较明显的活性,在500mg/L浓度时对稗草的株防效分别为51 3%和55 0%;对油菜株防效较弱,分别只有33 5%和17 5%。     

喹喔啉类化合物的合成研究进展

喹喔啉是一种重要的精细化工中间体,广泛用于农药,医药等行业,本文以二羰基,二硫代碳基,环氧化合物,α-羟基酮,α,β-二醇以及α-卤代酮与邻苯二胺为原料,综述了近些年来过渡金属与无过渡金属条件下喹喔啉合成方法的研究进展。报道了化学家们在合成喹喔啉这一领域里的合成方法,并对喹喔啉合成的研究前景进行了展望。     

2-多氟芳基喹喔啉衍生物的合成及制备工艺研究

以2-羟基喹喔啉衍生物为原料,通过溴化反应制备中间产物2-溴喹喔啉衍生物,与多氟芳烃在碘化亚铜的催化作用下发生偶联反应,合成了2-多氟芳基喹喔啉衍生物,产物结构经过了~1H NMR、~(13)C NMR、~(19)F NMR和MS表征。研究了催化剂种类及用量、物料比、反应温度、碱和溶剂对产物收率的影响。结果表明,2-多氟芳基喹喔啉衍生物优化工艺条件为:n(2-溴喹喔啉衍生物)∶n(多氟芳烃)∶n(碘化亚铜)∶n(1,10-菲啰啉):n(磷酸钾)=1.0∶1.5∶0.1∶0.1∶2.0,二甲苯-二甲基甲酰胺V/V=1/1为反应溶剂,在110℃下反应12 h,收率81%。     

2-多氟芳基喹喔啉衍生物的合成及制备工艺研究

以2-羟基喹喔啉衍生物为原料,通过溴化反应制备中间产物2-溴喹喔啉衍生物,与多氟芳烃在碘化亚铜的催化作用下发生偶联反应,合成了2-多氟芳基喹喔啉衍生物,产物结构经过了¹H NMR、1H NMR、⁽¹³⁾C NMR、(13)C NMR、⁽¹⁹⁾F NMR和MS表征。研究了催化剂种类及用量、物料比、反应温度、碱和溶剂对产物收率的影响。结果表明,2-多氟芳基喹喔啉衍生物优化工艺条件为:n(2-溴喹喔啉衍生物)∶n(多氟芳烃)∶n(碘化亚铜)∶n(1,10-菲啰啉):n(磷酸钾)=1.0∶1.5∶0.1∶0.1∶2.0,二甲苯-二甲基甲酰胺V/V=1/1为反应溶剂,在110℃下反应12 h,收率81%。     

空气氧化一锅法合成1,2,3,4-四氢吲哚[2,3-b]喹喔啉

为了探索喹喔啉新的合成路线,以吲哚醌和环己二胺为原料,在空气中氧气的作用下合成了1,2,3,4-四氢-6H-吲哚[2,3-b]喹喔啉,共合成衍生物12个,产率为39%~70%,所合成的化合物通过红外、核磁、质谱进行了表征。结果说明合成了目标产物。此外,对化合物9-氟-1,4-二氢-6H-吲哚喹喔啉(Ⅰl)和9-甲基-1,4-二氢-6H-吲哚喹喔啉(Ⅰm)进行了X射线衍射测试,对晶体结构进行了分析。     

1，4-二氧喹喔啉甲醛双腙的合成及除草活性研究

1，4-二氧喹喔啉类化合物是研究得较早的具有抗菌活性的物质，此类化合物的主要特点是低毒副作用和较明显抑菌活性，被广泛作为兽药和医药。所报道的化合物主要是1，4-二氧喹喔啉甲酸的衍生物如酯和酰胺类化合物，其醛衍生物的研究工作还少见报道，更未见该类化合物的除草活性的研究。     

Wild edible fruits as a potential source of phytochemicals with capacity to inhibit lipid peroxidation

The edible fruits of four wild small trees or shrubs (Arbutus unedo, Crataegus monogyna, Prunus spinosa, and Rubus ulmifolius) traditionally consumed in the Iberian Peninsula were studied to evaluate their potential for human nutrition, considering their content in bioactive compounds. Lipophilic phytochemicals, such as fatty acids and tocopherols, as well as some hydrophilic antioxidants, such as vitamin C and organic acids, were analyzed. In addition, the antioxidant activity, measured as lipid peroxidation inhibition (β‐carotene/linoleate and TBARS assays), was evaluated in each fruit. As far as we know, this is the first report relating to bioactive compounds in wild fruits with relation to the lipid peroxidation inhibition. Data revealed that these wild edible fruits are good sources of bioactive compounds as organic acids, vitamin C, tocopherols, and polyunsaturated fatty acids. They could be considered as functional foods or potential sources of bioactive compounds with antioxidant synergism effect, to be included as antioxidant food ingredients or in dietary supplements, mainly Rubus ulmifolius, due to its high content in tocopherols. This study provides useful and relevant information that justify tocopherols influence in the prevention of lipid peroxidation, due to the strong correlation observed (r>0.95) between these lipophilic bioactive compounds and the antioxidant activity.     

向日葵盘精油的化学成分及抗氧化活性

为明晰采收后向日葵盘精油的成分及其体外抗氧化活性，应用水蒸气蒸馏法提取采收后向日葵盘精油，利用气相色谱-质谱联用法（GC-MS）分析其化学成分，通过DPPH自由基和ABTS自由基清除法对精油的体外抗氧化活性进行测定。结果显示：从向日葵盘精油中共鉴定出49种化学成分（占精油总量91.16%），其中α-蒎烯（28.22%）、柠檬烯（6.55%）、α-蛇麻烯（4.99%）、反式-β-金合欢烯（3.58%）和莰烯（3.39%）为其主要成分。向日葵盘精油具有一定的体外抗氧化活性，其清除DPPH自由基、ABTS自由基的半数有效浓度（EC₅₀）值分别为0.47、0.30 g/L，明显高于阳性对照BHT的EC₅₀值（分别为8.21和6.16 mg/L）。     

In vitro antioxidant and anti-proliferation activities of polysaccharides from various extracts of different mushrooms

Polysaccharides were extracted from eight kinds of Chinese mushrooms using three solvents and were evaluated for their total carbohydrate, polyphenolic and protein contents, and antioxidant and anti-proliferation activities. The results suggested that all the polysaccharides had significant antioxidant capacities (EC(50) ranged from 1.70 ± 0.42 to 65.98 ± 1.74 μM TE/g crude polysaccharide inhibition of ABTS(+), EC(50) ranged from 5.06 ± 0.12 to 127.38 ± 1.58 mg VCE/g CP scavenging of OH· and EC(50) ranged from 0.70 ± 0.04 to 33.54 ± 0.49 mg VCE/g CP inhibition of lipid peroxidation) (TE: trolox equivalent; VCE: VC equivalent; CP: crude polysaccharide). The acid extracts of Russula vinosa Lindblad had the highest ABTS(+) scavenging activity. Aqueous extracts of Dictyophora indusiata and Hohenbuehelia serotina possessed, respectively, the highest OH· scavenging capacity and ability to inhibit lipid peroxidation. Mushroom extracts also inhibited proliferation of HeLa and HepG2 cells in a dose-dependent manner. These results indicate that the mushroom polysaccharides might be potential antioxidant resources.     

Action of 1-(11-selenadodecyl)-glycerol and 1-(11-selenadodecyl)-3-trolox-glycerol against lipid peroxidation

The antioxidant action on lipid peroxidation of the synthesized selenium compounds 1-(11-selenadodecyl)-glycerol (SeG) and 1-(11-selenadodecyl)-3-Trolox-glycerol (SeIrG, where Trolox=6-hydroxyl-2,5,7,8-tetramethylchroman-2-carboxylic acid) was investigated. We compared the reactivity of the selenium compounds toward peroxyl radicals and their inhibitory effect on lipid peroxidation, induced by several kinds of initiating species such as azo compounds, metal ions, and superoxide/nitric oxide in solution, micelles, membranes, and rat plasma. SeTrG, but not SeG, scavenged peroxyl radicals. SeG reduced methyl linoleate hydroperoxides in organic solution and in methyl linoleate micelles oxidized by ferrous ion (Fe²⁺)/ascorbic acid. In rat plasma SeG and SeTrG decreased the formation of lipid hydroperoxides generated by hydrophilic azo compounds. SeG and SeTrG spared α-tocopherol (α-TOH) consumption in multilamellar vesicle membranes oxidized by hydrophilic or lipophilic initiators, and only SeTrG spared α-TOH in superoxide/nitric oxide oxidized membranes. In rat plasma oxidized by radical initiators (either hydrophilic or lipophilic) or superoxide/nitric oxide, SeTrG suppressed α-TOH consumption, but SeG had no effect. The two selenium-containing compounds showed inhibitory effects on lipid peroxidation that depended on their structure, the medium where they acted, and the oxidant used.     

Development and validation of fluorescence spectroscopic assays to evaluate antioxidant efficacy. Application to metal chelators

Two fluorescence-based assays were developed for rapid evaluation of compounds for antioxidant activity. These assays were based on the quenching of intensity of the fluorescent probe and an increase in its fluorescence anisotropy due to the free radicals generated during lipid peroxidation. A large unilamellar vesicle system, containing the fluorescence probe diphenylhexatriene-propionic acid, was used to study the effects of chelators on metal-ion-induced lipid peroxidation. In this paper, the actions of the chelating agents ethylenediaminetetraacetic acid disodium salt (EDTA), nitrilotriacetic acid trisodium salt (NTA), adenosine-5′-diphosphate disodium salt (ADP), and sodium citrate on Fe(II)- and Fe(III)-induced peroxidation were compared. The effects of chelators on metal-ion-induced peroxidation depended on the type of metal used to initiate peroxidation and, for citrate, also on the concentration of chelator used. EDTA strongly suppressed both Fe(II)- and Fe(III)-induced peroxidation in this system. NTA and ADP inhibited Fe(III)-induced peroxidation but enhanced Fe(II)-induced peroxidation at all concentrations tested. Citrate promoted both Fe(II)- and Fe(III)-induced peroxidations at lower chelator-to-metal ratios; however, at higher ratios, it inhibited both peroxidations. The results of the two fluorescence-based assays agreed well with the quantitation of conjugated dienes and hydroperoxides by high-performance liquid chromatography. The combination of sensitivity, speed, and general utility associated with these methods suggests that these methods will be useful in rapid screening of extracts and purified compounds for antioxidant activity.     

Phytochemical and Biological Studies of Agave attenuata

The present study was conducted to examine various biological activities of a methanol extract of Agave attenuata leaves. GC-MS analysis of the n-hexane fraction from the extract revealed the presence of 31 compounds, with mono-2-ethylhexyl phthalate (11.37%), 1,2-benzenedicarboxylic acid (6.33%), n-docosane (6.30%) and eicosane (6.02%) as the major components. The leaves contained appreciable levels of total phenolic contents (10.541-39.35 GAE, mg/100 g) and total flavonoid contents (43.35-304.8 CE, mg/100 g). The extract and some of its fractions showed moderate antimicrobial effects. Leaves extract and fractions also exhibited a good antioxidant potential when measured by DPPH radical scavenging activity and inhibition of lipid peroxidation assays. The hemolytic effect of the plant was found to be in a range of 1.01%-2.64%. From the present study it is concluded that this plant could be used as a source of natural antioxidants and functional food nutraceutical applications.     

Protective effect of estrogens and catecholestrogens against peroxidative membrane damagein vitro

The antioxidant effects of natural estrogens (estrone E₁; 17β-estradiol), synthetic estrogens (17α-ethynylestradiol, EE₂; mestranol, MES; diethylstilbestrol, DES) and catechle-strogens (2-hydroxyestradiol; 4-hydroxyestradiol 4-OHE₂) on lipid peroxidation induced by different means in rat liver microsomes were investigated. The extent of lipid peroxidation was determined by measuring thiobarbituric acid reactive substances. Prooxidants included Fe³⁺/ADP/reduced NADPH, Fe²⁺/ascorbate,tert-butyl hydroperoxide (t-BOOH) and 2,2′-azobis (2-amidinopropane) (AAPH). Estrogens and catecholestrogens decreased lipid peroxidation in all four systems tested. In the iron/ascorbate model it was shown that (i)-OHE₂ and DES had analogous patterns of inhibition, irrespective of the presence of NADPH or the functional integrity of the microsómes, and (ii) the antioxidant activities of E₁, EE₂ and MES were dependent on the assay conditions with the activity being markedley higher when estrogen metabolism was favored. When peroxidation was initiated by the peroxyl radical generator AAPH, the inhibitory effects observed were least pronounced. Our data also showed that, in each of the systems, all inhibitors displayed the same order of inhibitory potency with DES and catecholestrogens being the most potent antioxidants under all experimental conditions used. The present results confirm earlier findings and point toward a link between estrogen metabolism and estrogen antioxidant activity. The data also indicate that estrogens and catecholestrogens interact with the peroxidative process at different levels with their interactions with iron or the metal-derived species being the most important modes of inhibition.     

丹皮总黄酮的提取及抗氧化活性研究

以丹皮为原料提取丹皮总黄酮,并测得其在丹皮中的含量为1.6304%。以常用的化学合成抗氧化剂2,6-二叔丁基-4-甲基苯酚(BHT)和叔丁基对苯二酚(TBHQ)为对照,通过4种方法评价了丹皮总黄酮的抗氧化活性。结果表明,在相同浓度条件下,丹皮总黄酮对羟基自由基(·OH)清除率对DPPH自由基(·DPPH)清除率对超氧阴离子自由基(·O-2)清除率对小鼠肝组织脂质过氧化的抑制率;丹皮总黄酮具有较强的抗氧化能力,其抗氧化活性略低于或等于TBHQ的抗氧化活性,远远大于BHT的抗氧化活性,在较低浓度下即具有对多种氧化反应的抑制作用。表明,丹皮总黄酮是一种很有发展前景的天然抗氧化剂。     

Protective activities of some phenolic 1,3-diketones against lipid peroxidation: possible involvement of the 1,3-diketone moiety

The protective activities of four ginger-derived phenolic 1,3-diketones (1-4) and curcumin (5) against lipid peroxidation was studied by using different biologically relevant model systems and pulse radiolysis. The extraordinary activity of 5 vis-à-vis 1-4 against Fe(2+)-mediated peroxidation may be attributed to the additional phenolic hydroxy group in the former, which lends it better iron-chelating and radical-scavenging properties. In iron-independent peroxidation, however, the ginger constituent [6]-dehydrogingerdione (1) showed activity comparable to that of 5; this indicates its higher affinity for the lipid peroxide radical (LOO(.)), due to its higher hydrophobicity. A very high rate constant for the reaction between 1 and Cl(3)COO(.), measured by pulse radiolysis, not only confirmed this, but also established the superior antioxidant efficacy of 1 in comparison to vitamins E and C. This was also evident from the results obtained from a liposomal peroxidation study with 1 and vitamin C. This study also established a synergistic effect of the latter on the antioxidant activity of 1. HPLC analysis of the products of the reaction between 1 and Cl(3)COO(.) revealed the formation of higher concentrations of ferulic acid (7), along with vanillin (6). The presence of ascorbate affected the generation of 7 more than it did that of 6. On this basis, a mechanism for the antioxidant action of 1 has been proposed, which suggests the contribution of the phenolic group as well as the active methylene group of the 1,3-diketones.     

Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging

The design of three novel fatty nitrogen mustard-based anticancer agents with fluorophores incorporated into the alkene structure(CXL 118,CXL121,and CXL122)is described in this report.The results indicated that these compounds are selectively located in lysosomes and exhibit effective antitumour activity.Notably,these compounds can directly serve as both reporting and imaging agents in vitro and in vivo without the need to add other fluorescent tagging agents.