3种根皮素酰腙衍生物的合成及抑制酪氨酸酶和抗氧化活性

以根皮素为母体,设计合成了三种新的酰腙类化合物1～3:根皮素苯甲酰腙(1)、根皮素2-羟基苯甲酰基腙(2)和根皮素4-羟基苯甲酰基腙(3).采用UV、IR、1H NMR、13C NMR及MS等手段对产物进行结构表征;测定了根皮素及其酰基腙的抑制酪氨酸酶的能力、清除DPPH自由基能力和清除ABTS自由基能力.结果表明化合物2(IC50 =13.4±1.1 μM)和化合物3(IC50=19.1±0.82μM)抑制酪氨酸酶能力比母体根皮素(IC50=23.7±1.8 μM)有了明显提高;化合物1～3清除DPPH和ABTS自由基的能力均得到显著提高;通过构效关系探讨,表明化合物芳酰基苯环上羟基数目和位置在抑制酪氨酸酶和清除自由基能力中发挥着重要作用.     

根皮素异烟酰基腙的合成、表征及抗氧化活性研究

本文旨在提高根皮素的生物活性,以其作为母体通过与异烟肼结合引入C=NNH活性基团,合成了一种新型酰腙类化合物。采用UV,IR,1H NMR,13C NMR及元素分析等手段对产物进行结构表征,并测定了根皮素及其异烟酰基腙的还原能力,清除DPPH自由基及清除ABTS自由基能力。结果表明根皮素异烟酰基腙的抗氧化活性显著优于根皮素。     

水飞蓟宾乳糖苷的合成、表征及抗氧化活性研究

实验设计旨在提高水飞蓟宾的水溶性、生物活性,以水飞蓟宾和乳糖苷为原料合成水飞蓟宾乙酰乳糖苷和水飞蓟宾乳糖苷.采用IR、1H NMR、13C NMR及HPLC-MS等手段对产物进行结构表征,并测定了水飞蓟宾乳糖修饰物的还原能力,清除DPPH自由基,清除ABTS+自由基能力及抑制脂质过氧化能力.结果表明水飞蓟宾乳糖苷的抗氧化活性显著优于水飞蓟宾.     

染料木素乙酰阿魏酸酯的合成

基于Schotten-Bamann反应原理,以阿魏酸和染料木素为起始原料,首次合成得到两种新化合物:染料木素-7-乙酰阿魏酸酯(即5-羟基-3-(4-羟苯基)-4-羰基-4H-苯并吡喃-7基3-(4-乙酰基-3-甲氧苯基)丙烯酸酯,1)和染料木素-7,4′-二-乙酰阿魏酸酯(即3-{4-[3-(4-乙酰氧基-3-甲氧苯基)丙烯酰氧基]苯基}-5-羟基-4-羰基-4H-苯并吡喃-7基3-(4-乙酰基-3-甲氧苯基)丙烯酸酯,2),对其进行了UV,IR,1H,13C NMR和MS结构表征.     

根皮素蛋氨酸希夫碱的合成及其性质研究

本研究旨在提高根皮素的溶解性和抗氧化活性。以根皮素为母体,在其结构上引入水溶性较好的蛋氨酸,合成了一种新型的根皮素衍生物——根皮素蛋氨酸希夫碱。采用UV、红外、1H NMR及MS对其结构进行了表征,并对根皮素及其衍生物的溶解性、抗氧化活性和稳定性进行了探讨。实验结果表明,与母体根皮素相比,根皮素衍生物的水溶性提高了约20倍,其抗氧化活性及在不同pH介质中的稳定性均优于根皮素。急性毒性实验的结果为小鼠LD505000 mg,属实际无毒。因此,在根皮素结构上引入蛋氨酸基团既提高其抗氧化性、溶解性和稳定性,又保证其安全性,为拓宽根皮素在食品和药品中的广泛应用提供新的途径。     

根皮素蛋氨酸希夫碱的合成及其性质研究北大核心CSCD

本研究旨在提高根皮素的溶解性和抗氧化活性。以根皮素为母体,在其结构上引入水溶性较好的蛋氨酸,合成了一种新型的根皮素衍生物——根皮素蛋氨酸希夫碱。采用UV、红外、1H NMR及MS对其结构进行了表征,并对根皮素及其衍生物的溶解性、抗氧化活性和稳定性进行了探讨。实验结果表明,与母体根皮素相比,根皮素衍生物的水溶性提高了约20倍,其抗氧化活性及在不同pH介质中的稳定性均优于根皮素。急性毒性实验的结果为小鼠LD50>5000 mg,属实际无毒。因此,在根皮素结构上引入蛋氨酸基团既提高其抗氧化性、溶解性和稳定性,又保证其安全性,为拓宽根皮素在食品和药品中的广泛应用提供新的途径。     

根皮素对HepG2肝癌细胞增殖和凋亡影响的实验研究

目的：探讨根皮素对人肝癌HepG2细胞增殖和凋亡的影响。方法：MTT法检测不同浓度（30、40、50 ug/mL）根皮素对肝癌 HepG2 细胞增殖的抑制作用,流式细胞技术检测根皮素对HepG2细胞凋亡的影响,ELISA 法检测不同浓度根皮素干预后细胞中 Bcl-2 和Bax表达的变化,Western blot法检测30 ug/mL根皮素在8,16,24 小时后检测p-AKT 蛋白表达情况。结果：30、40 和50 ug/mL 的根皮素对肝癌HepG2 细胞的增殖均有抑制作用（P＜0.01）,同时,30、40 和50 ug/mL 的根皮素在24 小时后可诱导 HepG2 细胞发生早期凋亡,凋亡率分别为0.1321± 0.0224, 0.2607± 0.0457, 0.3712± 0.0884（P＜0.01）;另外,30、40 和50 ug/mL的 根皮素作用24 小时后细胞内Bcl-2 表达降低,Bax 表达增高（P＜0.01）;最后,30 ug/mL根皮素可以明显减少p-AKT 表达量,这 种作用呈现时间依赖性。结论：根皮素能够抑制肝癌HepG2 细胞的增殖和促进细胞凋亡。     

川芎晒干过程中阿魏酸和阿魏酸松柏酯含量的变化

为了解新鲜川芎采后干燥过程中阿魏酸和阿魏酸松柏酯含量的动态变化规律,采用高效液相色谱法测定了川芎晒干过程中总阿魏酸、游离阿魏酸和阿魏酸松柏酯的含量。结果显示,在整个晒干过程中(30 d),总阿魏酸、游离阿魏酸和阿魏酸松柏酯含量呈先升高后下降的变化趋势,晾晒第3 d时总阿魏酸含量最高(0.23%),因此在晾晒的第3 d利用快速干燥技术能较好地保留川芎药材中总阿魏酸含量,使其发挥更佳的药效。川芎药材中的阿魏酸松柏酯能水解产生阿魏酸,因此研究川芎干燥过程中的生理响应与含水量的关系对阿魏酸积累有重要意义。由于川芎在用药过程中是以总阿魏酸含量发挥药效的,所以以总阿魏酸含量作为川芎药材质量控制指标更加科学。     

微生物合成根皮素及其糖苷研究进展 *

根皮素及其糖苷是二氢查耳酮类天然产物,具有抗氧化、抗炎和抑菌等多种生理活性,可应用于食品、药品、化妆品等行业。目前,根皮素及其糖苷主要从植物中提取,但含量低、组分复杂制约了高效、低成本的分离制备。随着合成生物学的发展,工程微生物生产根皮素及其糖苷将是一种有潜力的方法。综述了微生物合成根皮素及其糖苷的关键基因鉴定、代谢途径重构和优化策略,并针对酶的特异性差、副产物多等问题提出了技术对策。     

以中性红为电化学探针考察根皮苷、根皮素与DNA的作用

以中性红为电化学探针,采用循环伏安法考察了海棠叶提取产物根皮苷、根皮素与DNA的相互作用.在pH=4.1 的B-R缓冲溶液中,中性红在玻碳电极上产生一对明显的氧化还原峰.随着DNA的加入,NR的氧化还原峰电流ip明显下降,表明NR与DNA结合,溶液中游离的中性红减少.向体系中继续加入根皮苷(素),中性红的氧化还原峰回升,体系中游离的中性红增多.由于药物与中性红在DNA上有共同的结合位点,药物与DNA结合会游离出中性红.吸收光谱法证实了竞争结合的机制.在同样的实验条件下,根皮苷和根皮素与DNA结合的程度有明显差异,根皮素与DNA作用程度明显强于根皮苷.     

Effects of alcoholic solvents on antiradical abilities of protocatechuic acid and its alkyl esters

DPPH radical scavenging reactions of protocatechuic acid and its methyl ester were investigated in various solvents. In alcoholic solvents, methyl protocatechuate rapidly scavenged more than four equivalents of the radical, whereas approximately two equivalents were consumed in aprotic solvents. Methyl, ethyl, butyl, isopropyl, and tert-butyl protocatechuates were examined for their DPPH radical scavenging abilities in methanol or ethanol. As a result, the radical scavenging equivalence of sterically bulky esters tended to decrease compared to that of methyl or ethyl ester. The ABTS radical scavenging ability of those esters in water also showed the same tendency. Since 2-methoxy derivatives were detected in the reaction mixture of methyl protocatechuate and DPPH radical in methanol, a nucleophilic attack of an alcoholic molecule on the o-quinone intermediate, which is sensitive to steric hindrance from alkyl groups of both esters and alcoholic solvents, must be crucial for total radical scavenging abilities.     

In Vitro Antioxidant Profile of Phenolic Acid Derivatives

Several caffeic acid esters isolated from propolis exhibit interesting antioxidant properties, but their in vivo use is compromised by hydrolysis of the ester bond in the gastrointestinal tract. Therefore, a series of caffeic acid amides were synthesized and their in vitro antioxidant profile was determined. A series of hydroxybenzoic acids, hydroxycinnamic acids, and the synthesized caffeic acid amides were tested for both their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and microsomal lipid peroxidation-inhibiting activity. Some of the highly active antioxidants were further tested by means of electron paramagnetic resonance for their hydroxyl radical scavenging activity. Since a promising antioxidant compound should show a lipid peroxidation-inhibiting activity at micromolar level and a low cytotoxicity, the cytotoxicity of the phenolic compounds was also studied. In all the assays used, the caffeic acid anilides and the caffeic acid dopamine amide showed an interesting antioxidant activity.     

In vitro antioxidant profile of phenolic acid derivatives

Several caffeic acid esters isolated from propolis exhibit interesting antioxidant properties, but their in vivo use is compromised by hydrolysis of the ester bond in the gastrointestinal tract. Therefore, a series of caffeic acid amides were synthesized and their in vitro antioxidant profile was determined. A series of hydroxybenzoic acids, hydroxycinnamic acids, and the synthesized caffeic acid amides were tested for both their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and microsomal lipid peroxidation-inhibiting activity. Some of the highly active antioxidants were further tested by means of electron paramagnetic resonance for their hydroxyl radical scavenging activity. Since a promising antioxidant compound should show a lipid peroxidation-inhibiting activity at micromolar level and a low cytotoxicity, the cytotoxicity of the phenolic compounds was also studied. In all the assays used, the caffeic acid anilides and the caffeic acid dopamine amide showed an interesting antioxidant activity.     

Egyptian propolis: 3. Antioxidant,antimicrobial activities and chemical composition of propolis from reclaimed lands

The free radical scavenging effect of two propolis samples collected from reclaimed land, Egypt as well as of vitamin C and caffeic acid in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical system was determined. The antimicrobial (Staphylococcus aureus; Escherichia coli and Candida albicans) activity was also investigated. The results of the free radical scavenging effect of El-Saff and Ismailia propolis showed a concentration-dependent activity. The antioxidant activity was varied according to the examined material. It was obvious that caffeic acid and vitamin C showed the highest activity if compared with the propolis samples. El- Saff propolis had a higher antioxidant activity than Ismailia propolis, it showed a higher antibacterial activity against Staphylococcus aureus and a higher anti-fungal activity against Candida albicans. While the Ismailia propolis had a higher antibacterial activity against Escherichia coli, than El-Saff propolis. The chemical composition of propolis samples was investigated by GC/MS, where 75 compounds were identified, 22 being new for propolis. The Ismailia propolis was characterized by the presence of a highly significant amount of aromatic acid esters (47.3%) and triterpenoids (17.3%), while El-Saff propolis contained 3% and 1.9% respectively. The new esters belonged to 4-methoxyhydrocinnamic acid, hydroferulic acid and ferulic acid. El-Saff propolis had a very high significant amount (27%) of 2,6-bis-(pentanyloxy)-4-pentanylphenethanol, which is also a new compound for propolis.     

The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids

Phloretin is a dihydrochalcone flavonoid that displays a potent antioxidant activity in peroxynitrite scavenging and the inhibition of lipid peroxidation. Comparison with structurally related compounds revealed that the antioxidant pharmacophore of phloretin is 2,6-dihydroxyacetophenone. The potent activity of 2,6-dihydroxyacetophenone is due to stabilisation of its radical via tautomerisation. The antioxidant pharmacophore in the dihydrochalcone phloretin, i.e., the 2,6-dihydroxyacetophenone group, is different from the antioxidant pharmacophores previously reported in flavonoids.     

金属硫蛋白清除自由基及其对自由基引起的核酸损伤保护作用的研究

通过化学反应体系产生ＯＨ－和Ｏ自由基,采用荧光和化学发光检测体系,比较研究了不同亚型及不同结合金属的金属硫蛋白（ＭＴ）清除自由基能力的大小。结果表明,对于同一亚型,Ｚｎ结合ＭＴ清除自由基的能力大于Ｃｄ结合ＭＴ同一结合金属的ＭＴ,ＭＴ１清除自由基的能力大于ＭＴ２。通过比较ＺｎＭＴ１与谷胱甘肽（ＧＳＨ）及超氧化物歧化酶（ＳＯＤ）清除自由基的能力大小发现,ＺｎＭＴ１清除ＯＨ的能力是ＧＳＨ的１００倍,清除Ｏ自由基的能力分别是ＧＳＨ和ＳＯＤ的２５和０．０１倍。即ＭＴ是一种很好的ＯＨ自由基清除剂。以ＯＨ对核酸（ＤＮＡ）的损伤为例,研究了ＭＴ对核酸损伤的保护作用,其变化规律与上述结果相一致。     

金属硫蛋白清除自由基及其对自由基引起的核酸损伤保护作用的研究

通过化学反应体系产生ＯＨ＾－和Ｏ＾－２自由基,采用荧光和化学发光检测体系,比较研究了不同亚型及不同结合金属的金属硫蛋白（ＭＴ）清除自由基能力的大小。结果表明,对于同一亚型,Ｚｎ结合ＭＴ清除自由基的能力大于Ｃｄ结合ＭＴ;同一结合金属的ＭＴ,ＭＴ１清除自由基的能力大于ＭＴ２。通过比较ＺｎＭＴ１与谷胱甘肽（ＧＳＨ）及超氧化物歧化酶（ＳＯＤ）清除自由基的能力大小发现,ＺｎＭＴ１清除ＯＨ的能力是ＧＳＨ的１０     

Identification of chemical structure and free radical scavenging activity of diphlorethohydroxycarmalol isolated from a brown alga, Ishige okamurae

To obtain a natural antioxidant from a marine biomass, this study investigated the antioxidative activity of methanolic extracts from the marine brown alga, Ishige okamurae collected off Jeju Island. A potent free radical scavenging activity was detected in the ethyl acetate fraction containing polyphenolic compounds, and the potent antioxidant elucidated as a kind of phlorotannin, diphlorethohydroxycarmalol, by NMR and mass spectroscopic data. The free radical scavenging activities of the diphlorethohydroxycarmalol were investigated in relation to 1,1-diphenyl-2-picrylhydrazyl (DPPH), alkyl, and hydroxyl radicals using an electron spin resonance (ESR) system. The diphlorethohydroxycarmalol was found to scavenge DPPH (IC50=3.41 microM) and alkyl (IC50=4.92 microM) radicals more effectively than the commercial antioxidant, ascorbic acid. Therefore, these results present diphlorethohydroxycarmalol as a new phlorotannin with a potent antioxidative activity that could be useful in cosmetics, foods, and pharmaceuticals.     

Synthesis of N-hydroxycinnamoyl amide derivatives and evaluation of their anti-oxidative and anti-tyrosinase activities

Twelve N-hydroxycinnamoyl amino acid amide ethyl esters (CAES) were synthesized by using l-amino acid ethyl ester hydrochloride and corresponding cinnamic acid (ferulic acid, acetylferulic acid and caffeic acid) as raw materials in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-hydrochloride (EDC) and 1-hydroxybenzotriene (HOBt). The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities of CAES were evaluated. The anti-tyrosinase activities of N-feruloyl amino acid ethyl esters and the hydroxyl (OH) free radical scavenging activities of N-caffeoyl amino acid ethyl esters were also examined. DPPH free radical scavenging activity was shown in all CAES, of which N-caffeoyl amino acid ethyl esters demonstrated higher radical scavenging activity than N-feruloyl amide derivatives, and (E) -N-(caffeic acid)-l-glycinate ethyl ester (c₅) had the strongest ability to scavenge free radicals with an IC₅₀ value of 18.6 µM. The acetylferuloyl amino acid esters exhibited the highest tyrosinase inhibition activity among the tested amides.