Synthesis of Camptothecin-lO-O-glucoside Using an Engineered Oleandomycin Glucosyltransferase  

作　　者：ZHU Xuelin YE Qinmei WEN Chao CHEN Liping LIANG Guangping ZENG Ting ZHANG Dongmei JIANG Renwang 

机构地区：[1]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, P. R. China

出　　处：《Chemical Research in Chinese Universities》2018年第3期423-427,共5页高等学校化学研究（英文版）

基　　金：Supported by the National Natural Science Foundation of China（No. 81573315）, the Natural Science Foundation of Guangdong Province, China（No.2015A030313313）, the Guangzhou Industry University Collaborative Innovation Major Projects, China （No.201508030016） and the Natural Science Foundation of Hainan Province, China（No. 817307）.

摘　　要：Oleandomycin glycosyltransferase variant P67T/S132F/A242V（ASP） was used to convert 10-hydroxycamptothecin into camptothecin-10-O-glucoside, which was confirmed by spectral analysis. Compared to the previously reported results, the present study reached the conversion rate up to 80% through the optimization of reaction conditions. In addition, compared with 10-hydroxycamptotheein（HCPT）, camptothecin-10-O-glucoside inhibited the proliferation of Huh7 cells in a concentration-dependent manner and showed stronger antineoplastic effect but lower toxicity. Furthermore, camptothecin-10-O-glucoside induced more apoptotic cells as compared with the parent compound.Oleandomycin glycosyltransferase variant P67T/S132F/A242V（ASP） was used to convert 10-hydroxycamptothecin into camptothecin-10-O-glucoside, which was confirmed by spectral analysis. Compared to the previously reported results, the present study reached the conversion rate up to 80% through the optimization of reaction conditions. In addition, compared with 10-hydroxycamptotheein（HCPT）, camptothecin-10-O-glucoside inhibited the proliferation of Huh7 cells in a concentration-dependent manner and showed stronger antineoplastic effect but lower toxicity. Furthermore, camptothecin-10-O-glucoside induced more apoptotic cells as compared with the parent compound.

关 键 词：Camptothecin-10-O-glucoside 10-HYDROXYCAMPTOTHECIN Glycosylation GLUCOSYLTRANSFERASE Antineoplastic 

分 类 号：O657.3[理学—分析化学] O623.624[理学—化学]