生物催化介导的葛根素衍生化研究进展  

Research progress on the puerarin derivatization through biocatalysis

作　　者：王雪凝 孔建强 WANG Xue-ning;KONG Jian-qiang(State Key Laboratory of Bioactive Substance and Function of Natural Medicines and NHC Key Laboratory of Biosynthesis of Natural Products,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,国家卫生健康委员会天然药物生物合成重点实验室,北京100050

出　　处：《药学学报》2020年第7期1590-1603,共14页Acta Pharmaceutica Sinica

基　　金：重大新药创制科技重大专项(2018ZX09711001-006);中国医学科学院医学与健康科技创新工程(2016-I2M-3-012,2019-I2M-1-005);学科建设项目(201920100801)。

摘　　要：葛根素药理活性多样,临床上常用于心脑血管疾病的治疗,但也存在水溶解性差、生物利用度低等问题。结构修饰是改善药物性质的一种重要方法,基于酶法合成的生物催化因其高选择性而成为葛根素结构修饰的主要途径之一。迄今为止,生物催化可以实现葛根素的酰化、糖基化和羟基化等修饰,已开发出多种水溶解性和生物利用度得到改善的活性葛根素衍生物。本文以修饰基团为导向,综述了将全细胞和工具酶作为生物催化剂获得葛根素衍生物的研究进展,以期为葛根素类药物的进一步合成、开发提供新思路。Puerarin,also known as daidzein 8-C-glucoside,is a major isoflavone glycoside from Pueraria lobata.Puerarin has been shown to possess a variety of pharmacological activities.It has been widely used for the treatment of cardiovascular and cerebrovascular diseases.However,the further applications are limited due to its low water solubility and poor bioavailability.Structural modification is thus regarded as an efficient approach to improve the solubility and bioavailability of puerarin.Unlike chemical modifications,enzyme-assisted modifications,namely biocatalysis,is a promising alternative for the regioselective synthesis of puerarin derivatives due to its high selectivity.Up to date,acylation,glycosylation and hydroxylation of puerarin had been achieved through enzyme-based biocatalysis.Diverse active puerarin derivatives with improved solubility and bioavailability have been thus developed.Based on modification groups,this paper focused on the progress in the preparation of puerarin derivatives by biocatalysis,in which the whole-cells or pure enzymes were used as the biocatalysts.This article was expected to provide new ideas for the synthesis and development of puerarin drugs.

关 键 词：葛根素 生物催化 结构修饰 生物利用度 溶解度 

分 类 号：R931[医药卫生—生药学]