摘要
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（Yji C）,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IC50范围为9.41~111.21μmol/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。
Objective To improve the water solubility and biological activity of neoligans（magnolol and honokiol） and test the antitumor activity of the modified compounds. Methods The glycosylated products of magnolol and honokiol were obtained by enzymatic synthesis using a UDP-glycosyltransferase（Yji C） from Bacillus. The products were characterized by high-performance liquid chromatography（HPLC）, liquid chromatography-mass spectrometry（LC-MS）, and nuclear magnetic resonance（NMR） analysis. MTT assay was used to detect the growth inhibition of 4 human cancer cell lines induced by the compounds. Results We obtained two glucosides of neolignans（magnolol and honokiol） for the first time by enzymatic synthesis using a UDP-glycosyltransferase. Based on the spectroscopic data, the glucosides were identified as magnolol-2-O-β-D-glucopyranoside（1） and honokiol-4＇-O-β-D-glucopyranoside（2）. Compounds 1-4 exhibited moderate anti-proliferative activities against the 4 human cancer cell lines, with IC50 values ranging from 9.41 to 111.21 μmol/L. Conclusion The glycoslated products show enhanced water solubility and drug sensitivity against SMMC7721 cells, suggesting their value as potential therapeutic drugs.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2015年第11期1570-1574,共5页
Journal of Southern Medical University
基金
国家自然科学基金(81302671)
安徽省自然科学基金(1408085QH162)
安徽省高等学校省级优秀青年人才基金重点项目(2013SQRL048ZD)
蚌埠市科技发展指导性项目(20150329)~~
关键词
新木脂素
糖基转移酶
抗肿瘤活性
neolignan
glycosyltransferase
anticancer activity
