CRCU

Chemical Research in Chinese Universities ›› 2018, Vol. 34 ›› Issue (3): 423-427.doi: 10.1007/s40242-018-7309-9

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Synthesis of Camptothecin-10-O-glucoside Using an Engineered Oleandomycin Glucosyltransferase

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

  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
  • Received:2017-09-19 Revised:2017-12-25 Online:2018-06-01 Published:2018-01-15
  • Contact: ZHANG Dongmei, JIANG Renwang E-mail:trwjiang@jnu.edu.cn;dmzhang701@gmail.com
  • Supported by:
    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).

Abstract: Oleandomycin glycosyltransferase variant P67T/S132F/A242V(ASP) was used to convert 10-hydroxy-camptothecin 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-hydroxycamptothecin(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.

Key words: Camptothecin-10-O-glucoside, 10-Hydroxycamptothecin, Glycosylation, Glucosyltransferase, Antineoplastic