一株海洋放线菌发酵液抗肿瘤活性初探

用四氮唑蓝(MTT)法对96株海洋放线菌、细菌、真菌的发酵液进行细胞毒活性的筛选,结果显示13%的放线菌和3%的细菌发酵液具有细胞毒活性.其中放线菌ACMA006具有显著细胞毒活性,而且能抑制多种肿瘤细胞的生长.进一步用DNAladder电泳分析和荧光染色法观察到放线菌ACMA006发酵液能明显诱导肿瘤细胞凋亡.这株具有抗肿瘤潜力的放线菌ACMA006值得进一步开发研究.     

2-取代-5-氟脲嘧啶的_β-D -木糖苷的合成(英文)

通过相转移催化法或ｋｏｅｎｉｇｓｋｎｏｒｒ’ｓ 反应合成了１１ 种未见文献报道的２取代５氟尿嘧啶的βＤ木糖苷,结构经ＩＲ、ＨＮＭＲ、ＭＳ或元素分析证实,初步生物实验表明具有一定程度的抗癌性。     

海带中岩藻黄素异构体的分离纯化及其体外抗肿瘤活性研究

海带采用乙醇提取色素,通过柱层析分离纯化其中的岩藻黄素,并最终通过高效制备液相色谱制备了三种岩藻黄素的异构体。通过紫外光谱(UV)、核磁共振氢谱(1H-NMR)以及质谱(MS)对岩藻黄素及其异构体进行了结构表征和鉴定。采用乳腺癌细胞MDA-MB-231模型,对岩藻黄素的体外抗肿瘤活性进行了研究。结果表明,岩藻黄素对乳腺癌细胞生长有显著的抑制作用,其中13-顺和13′-顺岩藻黄素组分对癌细胞的抑制活性最强, IC50值达到23.71μg/mL。全反式岩藻黄素和9′-顺岩藻黄素两种异构体IC50值分别为45.30和27.09μg/mL。qPCR试验表明岩藻黄素各异构体可以通过抑制癌细胞NF-κB家族基因表达而抑制乳腺癌细胞生长。     

老鼠簕植物内生真菌Aspergillus terreus (W-8)抗肿瘤活性成分的研究

对红树林植物的枝干、枝叶样品进行微生物分离,以P388细胞为模型进行活性评价得到14株具有抗肿瘤活性的真菌。采用溶剂萃取、柱色谱及半制备HPLC等分离手段对来源于红树林植物老鼠簕Acanthus ilicifolius Linn.的菌株Aspergillus terreus(W-8)发酵产物进行了活性追踪分离,共得到5个化合物。通过理化性质及波谱技术,结合文献,鉴定其结构分别为aspulvinone H1(1)、aspulvinone H(2)b、utyrolactone I(3)t、errein(4)和3-propylbenzene-1,2-diol(5),其中化合物1的核磁数据为首次报道。采用MTT法初步评价了单体化合物的抗肿瘤活性,结果表明化合物4、5对A549、K562和Hela细胞均具有中等强度的细胞毒活性。     

Isolation and pharmacological activities of bromophenols from Rhodomela confervoides

Four bromophenols were isolated from the extract of marine red alga, Rhodomela confervoides by column chromatography and HPLC methods. By means of spectroscopic methods including IR, MS, 1D, and 2D-NMR techniques, their structures were elucidated as (1) 3-bromo-4,5-dihydroxy benzoic acid methyl ester; (2) his (2,3-dibromo-4,5-dihydroxybenzyl) ether; (3) 3,4-dibromo-5-(methoxymethyl)-1,2-benzenediol and (4)3-bromo-4,5-dihydroxy-benzaldehyde. Compound 1 was first isolated from the algae in nature, and 1, 4 were found to have selective cytotoxic activities against KB, Bel 7402 and A549 cells, 2 showed powerful antibacterial activities against Staphylococcus aurens and Pseudomonas aeruginosa.     

The Antitumor Components from Marine-derived Bacterium Streptoverticillium luteoverticillatum 11014 Ⅱ

Eight known compounds were isolated from a marine-derived bacterium Streptoverticillium luteoverticillatum 11014 using bioassay-guided fractionations. Their structures were identified by spectral analysis as bis (4-hydroxybenzyl) ether (1), p-hydroxyphenylethyl alcohol (2), N-(4-hydroxyphenethyl) acetamide (3), indole-3 carboxylic acid methyl ester (4), dibenzo[b,e] [1,4]dioxine (5), thymine (6), cytosine deoxyribonucleoside (7) and 2, 3-butanediol (8). These compounds were evaluated for their cytotoxic activities against K562 cell line with the SRB method for the first time. Compounds 2 and 4 showed cytotoxcities with IC50 values of 101.1 and 165.3 μmolL-1, respectively. All compounds were isolated from S. luteoverticillatum 11014 for the first time.     

海绵微生物的分离培养及一种活性代谢产物的初步研究

研究海绵来源真菌Aspergillus repens发酵产物中的活性代谢产物.分离培养微生物进行活性筛选,采用活性追踪的方法、利用色谱手段分离获得单体化合物,根据波谱分析及其理化性质确定其结构,利用SRB评价单体化合物的抗肿瘤活性,利用纸片法测定单体化合物的抗植物病菌活性.获得1个萘并吡喃酮化合物,其结构鉴定为3,4-二氢-9,10-二羟基-7-甲氧基-3-甲基-1H-萘并[2,3c]吡喃-1-酮 (Semivioxanthin).该化合物对肿瘤细胞A-549、HL-60和BEL-7402有一定抑制作用,对植物致病菌作用较强.海绵微生物代谢产物是发现活性物质重要资源,值得深入研究.     

文蛤多肽的体外抗癌活性研究

采用硫酸铵沉淀、有机溶剂分离、Sephadex G-25分子筛层析等实验方法，从文蛤肉中提取了一种低分子量的多肽，命名为Mer2．本文以溴化二苯偶氮盐（MTT）法检测Mer2对体外培养的癌细胞的抑制作用．结果表明Mer2对体外培养的人肝癌细胞株（HepG2）、宫颈癌细胞株（Hela）、胆管癌细胞株（QBC939）、肺癌细胞株（SPC—A-1和LTEP—a-2）的生长均有很强的抑制作用，且抑制效果随着Mer2含量的增高和处理时间的延长而增强，证明Mer2具有广谱的抗癌活性．其中Mer2对人肝癌HepG2细胞株抑制作用最为显著，光学显微镜观察经Mer2细胞培养液处理后的细胞形态发生明显的改变，流式细胞仪实验的结果表明处理后的细胞周期发生明显的改变，并在G0／G1期前出现凋亡峰．     

The antitumor effect of bromophenol derivatives <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">Leathesia nana</Emphasis> extract <Emphasis Type="Italic">in vivo</Emphasis>

To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (1), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (2), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethyl-pyrocatechol (3), 2,2′,3,3′-tetrabromo-4,4′,5,5′-tetrahydroxy-diphenylmethane (4), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), 2,2′,3-tribromo-3′,4,4′,5-tetrahydroxy-6′-ethyloxymethyldiphenylmethane (6) were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTT assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Bel7402 and HCT-8. Their inhibitory activity against protein tyrosine kinase (PTK) with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana (EELN) was evaluated on S₁₈₀-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC₅₀ below 10 μg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4%, respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer. Supported by the National High Technology Research and Development Program of China (863 Program, No. 2007AA09Z410) and Knowledge Innovation Program of Chinese Academy of Sciences (No. KZCX2-YW-209)     

海藻抗肿瘤物质的筛选及其活性研究概况

国际上海洋药物研究的热潮自20世纪60年代开始，20世纪70-80年代开展了大规模筛选，迄今为止发现具有抗肿瘤、抗病毒、抗心血管疾病、增强免疫系统等活性的海洋生物活性物质5000余种。海洋天然产物的药理活性侧重于抗肿瘤方面，从海藻中发现的抗肿瘤活性物质占有重要的地位，因为海藻具有较好的生物多样性，而且其多变的生态环境和原始的进化地位使其拥有许多结构独特的活性物质，其研究始于巨大鞘丝藻的脂溶性提取物抗白血病活性的发现。20世纪80年代初美国和日本的科学家开始系统地筛选海藻的抗肿瘤活性物质，发现了许多新的化合物，如从松香藻中分离的Halomon，Scytophycin B目前已进入临床前药理评估阶段。 海洋药物的发展首先应着重可再生资源的开发和利用方面的研究，而海藻是一种取之不尽的药源物质，随着现代化生物技术的发展，特别是生物工程技术的发展和应用，基本上解决了药源藻类的养殖问题，为海藻抗肿瘤物质的研究提供了充足的材料和可行性，迄今海藻抗肿瘤生物活性物质的研究已取得了引人注目的成就。本文根据有关文献着重就海藻中抗肿瘤活性物质的筛选，以及相应的活性化合物作一综述。