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1. chinaXiv:201801.00699 [pdf]

酶法糖基化合成一种新型补骨脂定葡萄糖苷

李静; 李楠; 赵玉茹; 戴轶群; 霍强; 马涛; 李红梅; 吴成柱
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Objective To modify the structure of psoralidin using in vitro enzymatic glycosylation to improve its water solubilityand stability. Methods A new psoralidin glucoside (1) was obtained by enzymatic glycosylation using a UDP-glycosyltransferase. The chemical structure of compound 1 was elucidated by HR-ESI-MS and nuclear magnetic resonance(NMR) analysis. The high-performance liquid chromatography (HPLC) peaks were integrated and sample solution concentrations were calculated. MTT assay was used to detect the cytotoxicity of the compounds against 3 cancer cell lines in vitro. Results Based on the spectroscopic data, the new psoralidin glucoside was identified as psoralidin-6',7-di-O glucopyranoside (1), whose water solubility was 32.6-fold higher than that of the substrate. Analyses of pH and temperature stability demonstrated that compound 1 was more stable than psoralidin at pH 8.8 and at high temperatures. Only psoralidin exhibited a moderate cytotoxicity against 3 human cancer cell lines. Conclusion In vitro enzymatic glycosylation is a powerful approach for structural modification and improving water solubility and stability of compounds.

submitted time 2018-01-25 From cooperative journals:《南方医科大学学报》 Hits1497Downloads836 Comment 0

2. chinaXiv:201712.00734 [pdf]

新木脂素的酶法糖基化及抗肿瘤活性

李红梅; 李静; 靳伟; 郭星; 李楠; 马涛; 霍强; 吴成柱
Subjects: Medicine, Pharmacy >> Preclinical Medicine

目的 以厚朴酚与和厚朴酚为底物,进行酶法糖基化修饰以及检测其抗肿瘤活性,提高新木脂素类化合物(厚朴酚与和厚朴酚)的水溶性和生物活性。方法 利用来源于Bacillus的糖基转移酶(YjiC),通过酶法糖基化制备厚朴酚与和厚朴酚糖基化产物;经高效液相色谱(HPLC)、液相串联质谱(LC-MS)、核磁共振(NMR)检测分析鉴定其结构;通过MTT法检测药物对多种肿瘤细胞的增殖抑制效应。结果 利用酶法糖基化反应制备了2个新木脂素(厚朴酚与和厚朴酚)糖基化产物,并显著提高了其水溶性;糖基化产物分别鉴定为magnolol-2-O- β-D-glucopyranoside(1)和 honokiol-4'-O-β-D-glucopyranoside(2);MTT结果显示,厚朴酚与和厚朴酚及其糖基化产物对4种肿瘤细胞均表现出较强的抑制细胞增殖的作用,且呈现浓度依赖性,其IC 50 范围为9.41~111.21 ?mol/L。结论 厚朴酚与和厚朴酚糖基化产物显著提高水溶性以及增加了药物对SMMC7721细胞的敏感性,并具有良好的应用前景。

submitted time 2017-12-07 From cooperative journals:《南方医科大学学报》 Hits1055Downloads633 Comment 0

3. chinaXiv:201712.01137 [pdf]

Hsp90抑制剂梗如酸对乳腺癌MDA-MB-231细胞增殖、侵袭、迁移的影响

李红梅;聂丽娟;霍强;赵素容;马涛;吴成柱;刘浩
Subjects: Medicine, Pharmacy >> Preclinical Medicine

目的探讨热体克蛋白90 (Hsp90)抑制剂槚如酸对人乳腺癌MDA-MB-231细胞增殖、侵袭、迁移的影响。方法采用体外malachite green-molybdate显色反应和ATP一琼脂糖凝胶结合实验检测槚如酸对Hsp90抑制活性;MTT法检测药物对MDA-MB-231增殖抑制效应;Transwell小室法检测药物对细胞侵袭和迁移影响;免疫印迹法检测药物对相关蛋白基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1 (TIMP-1) ,Hap90、热体克蛋白70 ( Hsp70 )表达的影响。结果槚如酸为特异性的Hsp90抑制剂,其抑制IC50值为82.5μmol/L。MTT结果显示,槚如酸具有明显抑制细胞增殖的作用,且呈现浓度依赖关系,其IC50值为29.3μmol/L。不同浓度的槚如酸(12.5,25.0,50.0μmol/L)处理36 h后,与对照组相比,药物对细胞侵袭抑制率分别为:23.6%,56.6%,67.0%,P<0.05。槚如酸(12.5,25.0,50.0μmol/L)处理24 h后,与对照组相比,药物对细胞迁移抑制率分别为:30.0% ,45.5 % ,77.5 % , P<0.05。免疫印迹法结果显示,槚如酸随着浓度的增加,诱导MMP-9降解越明显,而对Hsp90和Hsp70蛋白表达均没有影响。结论槚如酸能明显抑制乳腺癌细胞增殖、侵袭、迁移能力,其机制可能是通过抑制Hsp90 ATPase活性以及导致下游的顾客蛋白的MMP-9表达下调有关。

submitted time 2017-12-07 From cooperative journals:《南方医科大学学报》 Hits807Downloads473 Comment 0

4. chinaXiv:201712.01203 [pdf]

化学修饰赋予肝素低抗凝血活性和高抗肿瘤活性

梁颖(1,2);李立标(3);张配(1,2);吴成柱(1,2);赵素容(1,2);张倩雯(1,2);刘浩(1,2);蒋志文(1,2)
Subjects: Medicine, Pharmacy >> Preclinical Medicine

目的对肝素进行化学修饰改造,并检测化学修饰物的抗凝血活性和抗肿瘤活性。方法用高碘酸钠氧化、硼氢化钠还原法降解普通肝素(I7FH ),并用大位阻二环己基碳二亚胺(DCC )和二甲氨基毗pi}(DMAP)为催化剂对所获低分子量肝素((LMWH)进行乙酸化修饰,获得低抗凝活性的乙酸化低分子肝素(ALMWH)。分别在小鼠和MDA-MB-231和MCF-7人乳腺癌细胞株检测ALMWH的抗凝血活性和抗肿瘤细胞增殖和侵袭活性。结果ALMWH的抗凝血活性显著降低,市售低分子肝素((LMWH*)延长凝血时间((CT)1倍的浓度为33.04 wmol"L-',ALMWH延长CT 1倍的浓度为223.56 wmol"L-',ALMWH将小鼠凝血时间延长1倍所需的药物浓度提高到LMWH*的6倍之多。0.1,0.3,0.9,2.7,8.1 mmol"L-'系列浓度的ALMWH和LMWH对人乳腺癌细胞MDA-MB-231和MCF-7的增殖均表现出显著的剂量依赖性抑制作用。但两药的抑制人乳腺癌细胞增殖强度具有明显的差异。LMWH和ALMWH的半数抑制MCF-7增殖浓度(ICso)分别为3168.4 wmol " L-'和152.6 wmol " L-',半数抑制MDA-MB-231增殖的IC分别为12299.6 wmol " L-'和22.2 wmol"L-'。化学修饰将LMWH抑制MCF-7的ICs)和抑制MDA-MB-231的IC分别降低了20和560倍。ALMWH和LMWH对于MDA-MB-231细胞的侵袭能力具有明显的抑制作用,统计学分析未发现二者抑制强度上的明显差异。结论结构的化学修饰可降低LMWH的抗凝血活性,增强其抗癌细胞增殖和侵袭活性。

submitted time 2017-12-07 From cooperative journals:《南方医科大学学报》 Hits978Downloads615 Comment 0

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