Zhu Jianhua, Chen Lijia, Hu Xianjing, Song Liyan, Wang Mingxuan, Yu Rongmin
Biotechnological Institute of Chinese Materia Medica, Jinan University, China ; Department of Natural Medicinal Chemistry, Jinan University, Guangzhou 510632, China.
Biotechnological Institute of Chinese Materia Medica, Jinan University, China.
Pharmacogn Mag. 2015 Jul-Sep;11(43):518-23. doi: 10.4103/0973-1296.160460.
The biosynthesis of artemisinin derivatives is one of the interesting subjects. Artemisinic acid (AA) has been widely studied as a supposed intermediate in the biosynthetic pathway leading to artemisinin in Artemisia annua.
To investigate the bioconversion of AA by transgenic crown galls of Panax quinquefolium.
AA was administered into crown galls of P. quinquefolium and co-cultured for 2 days. The methanol extract was separated by column chromatography, and the structures of two biosynthesis products were elucidated by physicochemical and spectroscopic methods. Co-culture time curves on conversion were also established. In addition, the effects of AA on the growth and ginsenosides production of crown galls of P. quinquefolium were investigated. Furthermore, the in vitro antitumor activities of AA and two glycosides against HepG2 cell line were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay.
Glycosylation of AA by crown galls of P. quinquefolium was observed, and two region-selectively glycosylated products were obtained (AA-1, AA-2), involving one new compound (AA-2). Their structures were elucidated to be AA β-D-glucopyranosyl ester (AA-1) and AA β-D-glucopyranosyl-(2 → 1)-β-D-glucopyranosyl ester (AA-2). The maximum yield of AA-1 was 19.3% on the 1(st) co-culture day while that of AA-2 was 59.1% on the 2(nd) day. MTT assay showed that the activity of monosaccharide glycoside (AA-1) was better than that of disaccharide glycoside (AA-2).
Two AA glycosides involved one new compound with potential antitumor activity were obtained by region-selective biosynthesis with crown galls of P. quinquefolium.
青蒿素衍生物的生物合成是一个有趣的研究课题。青蒿酸（AA）作为青蒿中通向青蒿素生物合成途径的假定中间体已被广泛研究。
研究西洋参转基因冠瘿对青蒿酸的生物转化作用。
将青蒿酸加入西洋参冠瘿中，共培养2天。甲醇提取物经柱色谱分离，通过理化和光谱方法鉴定两种生物合成产物的结构。还建立了转化的共培养时间曲线。此外，研究了青蒿酸对西洋参冠瘿生长和人参皂苷产生的影响。进一步通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法评估青蒿酸和两种糖苷对肝癌细胞系HepG2的体外抗肿瘤活性。
观察到西洋参冠瘿对青蒿酸进行糖基化，得到两种区域选择性糖基化产物（AA-1、AA-2），其中包括一种新化合物（AA-2）。其结构经鉴定为青蒿酸β-D-吡喃葡萄糖酯（AA-1）和青蒿酸β-D-吡喃葡萄糖基-(2→1)-β-D-吡喃葡萄糖酯（AA-2）。AA-1在第1天共培养时的最大产率为19.3%，而AA-2在第2天的最大产率为59.1%。MTT法显示单糖糖苷（AA-1）的活性优于二糖糖苷（AA-2）。
通过西洋参冠瘿的区域选择性生物合成获得了两种含潜在抗肿瘤活性新化合物的青蒿酸糖苷。
