几种喜树碱-糖缀合物的合成及其抗肿瘤活性研究

以喜树碱为母体,分别以甘氨酸和己二酸为连接臂与喜树碱的20-羟基以酯键缩合,再将其分别与半乳糖、甘露糖、乙酰氨基葡萄糖、乳糖的衍生物缩合定向半合成了3个水溶性(4-6)和1个脂溶性的喜树碱-糖缀合物(7),通过核磁共振氢谱、碳谱和高分辨质谱对化合物结构进行了确证。对已有的α构型喜树碱糖缀合物(1-3)和本文合成的β构型的喜树碱糖缀合物(4-7)的构效关系进行了初步的探讨,体外抗肿瘤实验表明,水溶性糖缀合物(1-6)具有与喜树碱相当的活性,脂溶性糖缀合物(7)的活性有明显下降。     

相转移催化法制备抗癌新药工艺

提出采用相转移催化法,一步合成了抗癌新药ASF。工艺条件达到最简。利用正交实验法确定了最佳反应条件,通过一系列分析手段确定产物结构。     

赤魟尾刺提取物的抗肿瘤作用

赤缸Dasyatis akajei（Muller＆henle）隶属于软骨鱼纲，下孔总目，鲼形目，魟科，魟属，常栖息于底质为泥沙的深潭中。赤魟肉性昧甘、咸平，有补气之功效。用其熬油，主治小儿疳积。尾刺研末入药，对治疗胃癌、食道癌、肺癌、乳腺炎、咽喉炎、疟疾、牙痛、魟鱼尾刺刺伤均有一定疗效。赤魟尾刺含有多种毒素，有重要药理作用。涂洪斌等克隆出编码赤魟肿瘤抑制因子IPL的全长cDNA序列，并报道了赤魟亲环素A的融合表达、纯化及活性特征。     

海绵共附生放线菌SH6004菌株中抗肿瘤活性成分的研究

研究共附生微生物,采用活性追踪的方法从1株海绵共附生放线菌SH6004的乙酸乙酯提取物中分离得到7个化合物,根据化合物的光谱特征和理化性质分别鉴定为N-甲基苯甲酰胺(1),2-苯甲酰氧基乙酸(2),对羟基苯乙酰胺(3),N-[2-(4-羟基苯基)乙基]乙酰胺(4),环-(丙-异亮)(5),尿嘧啶-2′-脱氧核苷(6)和胸腺嘧啶-2′-脱氧核苷(7).并利用SRB(丽丝胺罗丹明B)法,对7个单体化合物的体外抗肿瘤活性进行了初步评价,其中化合物3、6和7显示了弱的抗肿瘤活性.     

Studies on the antitumor activity and isolation of the glycoprotein from the gonad ofChlamys (Azumapecten) farreri

After being degreased with acetone, the female gonad ofChlamys (Azumapecten) farreri was extracted with water, and then subjected to DEAE—cellulose column chromatography and purified by Sephadex G-100 chromatography to obtain a pure female gonad glycoprotein (FGGP). The IR spectra, electrophoresis and chemical analysis of FGGP indicated that it was a kind of acid glycoprotein and that the content of total protein and sugar were 54.8% and 40%, respectively. Pharmacological tests showed that FGGP could inhibit (inhibition rate of 40.87%) the growth of Sarcoma 180 of mice.     

Evaluation of antitumor, immunomodulatory and free radical scavenging effects of a new herbal prescription seaweed complex preparation

Seaweed Complex Preparation (SCP) is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and digestive cancer. However, little information is available about the pharmacodynamic basis. The antitumor, immunomodulatory and free radical scavenging effects of SCP were evaluated in this study. Transplanted tumor in vivo method was used to determine the antitumor effect. The effects on splenocyte proliferation and phagocytosis of macrophages in tumor-bearing mice were measured by the MTT method and the phagocytizing cock red blood cell (CRBC) method respectively. The scavenging activities of SCP on DPPH and hydroxyl radicals in vitro were investigated. It was found that the medium-dose and high-dose of SCP could significantly inhibit the growth of transplanted hepatic tumor of murine hepatocarcinoma cell line H22, and promote proliferation of splenocytes and phagocytosis of macrophages. SCP possessed noticeable scavenging activities on DPPH and hydroxyl radicals. The antitumor effects of SCP might be achieved by improving immune system and scavenging free radicals, which is in accordance with the viewpoint of traditional Chinese medicine in promoting the body resistance and eliminating pathogenic factors for cancer treatment.     

The antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo

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 MTr 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 bromophenoi 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.     

海洋放线菌ACMA006抗肿瘤活性成分的分离纯化及结构鉴定

对从中国江苏连云港海域中筛选出的海洋放线菌ACMA006的发酵产物进行了分离纯化,获得2种抗肿瘤活性化合物,并进一步鉴定其结构．海洋放线菌ACMA006经大规模发酵后,发酵液采用溶剂萃取法提取其中的抗肿瘤活性成分,并利用硅胶柱层析、制备薄层及HPLC等方法对萃取物进行分离得到单体化合物．利用红外光谱、质谱、核磁共振‘H—HMR谱和”C—NMR谱等波谱数据对单体化合物的结构进行解析和鉴定．结果表明化合物B为放线菌素D,其分子式为c62：H86N12016含有2个多肽酯环,由L一苏氨酸、D一缬氨酸、L．脯氨酸、N一甲基甘氨酸和L—N一甲基缬氨酸组成,通过羧基与发色母核吩唾嗪酮相连接．化合物A可能为放线菌素D的衍生物．这是国内外首次从海洋放线菌中分离提取出放线菌素D．     

Antitumor and immune regulation activities of the extracts of some Chinese marine invertebrates

Extracts of 21 marine invertebrates belonging to Coelenterata, Mollusca, Annelida, Bryozoa,Echiura, Arthropoda, Echinodermata and Urochordata were screened for the studies on their antitumor and immune regulation activities. Antitumor activity was determined by MTT method and immune regulation activity was studied using T- and B-lymphocytes in mice spleen in vitro. It was found that the n-butanol part of Asterina pectinifera, the acetic ether part of Tubuaria marina, 95% ethanol extract of Acanthochiton rubrolineatus have a high inhibition rate of 96.7%, 63.9% and 50.5% respectively on tumor cell line HL-60 at the concentration of 0.063 mg/ml. The inhibition rate of the acetic ether part of Tubuaria marina on the tumor cell line A-549 is 65,4 % at concentration of 0.063 mg/mL. The 95% ethanol extract of Meretrix meretrix has so outstanding promoting effect on T-lymphocytes that their multiplication increases 25% when the sample concentration is only 1μg/ml. On B-lymphocytes, the 95% extract of Rapana venosa, at concentration of 100μg/ml, has a promotion percentage of 60%. On the other hand, under the condition of no cytotoxic effect, the 95% ethanol extracts of Acanthochiton rubrolineatus and Cellana toreum can reach 92% inhibition rate on T lymphocyte at concentration of 100μg/ml, while the inhibition rate on B lymphocyte of the 95% extract of Acanthochiton rubrolineatus reaches 92% at the same concentration.     

海洋真菌Neosartorya fischeri 1008F1的次级代谢产物抑菌及抗肿瘤活性的研究

通过抑菌及抗肿瘤活性实验,明确海洋真菌Neosartorya fischeri 1008F1次级代谢产物中的活性有效组分。应用对峙培养法和生长速率法,对菌株的抑菌活性进行测定。应用MTT法,对菌株的抗肿瘤活性进行测定。应用凝胶(Sephadex LH-20)柱层析的方法,对菌株发酵产物的提取物进行分离。结果发现,海洋真菌Neosartorya fischeri 1008F1的水溶性提取物对番茄早疫菌(Alternaria solani)具有一定的抑制活性。菌株的粗提物浸膏经Sephadex LH-20柱梯度洗脱后,得到的组分B、C、D、E和F。在0.5 g/L的供试浓度下,组分B、C和D对胃癌细胞SGC-7901的抑制率均高于80%,而组分B、C、D、E和F对肝癌细胞BEL-7404的抑制率均高于70%。