ACLY抑制剂脱氢弯孢霉菌素肝微粒体代谢  

Liver microsomal metabolism of dehydrocurvularin,an ACLY inhibitor

作　　者：周富贵 李玉兰 蔡晓蓉 薛莲 邓张双[1] ZHOU Fugui;LI Yulan;CAI Xiaorong;XUE Lian;DENG Zhangshuang(Hubei Key Laboratory of Natural Products Research and Development,College of Biological and Pharmaceutical Sciences,China Three Gorges University,Yichang 443002,Hubei,China;The First Clinical Medical College of China Three Gorges University,Yichang Center People s Hospital,Yichang 443003,Hubei,China;Three Gorges Public Inspection and Testing Center,Yichang 443000,Hubei,China;HEC API Yichang Co.,Ltd.,Yichang 443311,Hubei,China)

机构地区：[1]三峡大学天然产物研究与利用湖北省重点实验室,湖北宜昌443002 [2]宜昌市中心人民医院三峡大学第一临床医学院,湖北宜昌443003 [3]三峡公共检验检测中心,湖北宜昌443000 [4]宜昌东阳光制药有限公司,湖北宜昌443311

出　　处：《华中师范大学学报（自然科学版）》2022年第5期827-833,共7页Journal of Central China Normal University：Natural Sciences

基　　金：国家自然科学基金项目(31100080).

摘　　要：该文主要研究了潜在抗肿瘤候选化合物脱氢弯孢霉菌素的体外肝微粒体代谢特点.建立了脱氢弯孢霉菌素含量的HPLC测定方法,考察了脱氢弯孢霉菌素在不同种属来源的肝微粒体中的代谢速率差异.依据UPLC-MS结果推测脱氢弯孢霉菌素中α、β不饱和双键经环氧化反应,亲和反应和分子内脱水反应,生成epoxycurvularin、10,11-邻二羟基弯孢霉菌素和curvulopyran,且脱氢弯孢霉菌素在溶液中可能发生非酶催化的化学转化.考虑到脱氢弯孢霉菌素结构中的α,β不饱和双键既是重要的活性结构又是主要的代谢位点,合理的前药设计可能是提高该化合物可药性的有效方法.The hepatic metabolic characteristics of dehydrocurvularin,an antitumor candidate compound,were studied in this paper.HPLC was adopted in the content determination of dehydrocurvularin to study the metabolic rate in different liver microsomes.Dehydrocurvularin was suggested be converted to epoxycurvularin,10,11-ortho-hydroxycurvularin and curvulopyran through epoxidation,hydrotion reaction and intramolecular dehydration according to the UPLC-MS results.And there might be no-enzyme transformation of dehydrocurvularin in aqueous solution.Considering the fact that theα,βunsaturated double bond is the important active structure as well as main metabolic site,reasonable prodrug design would be an effective method to improve the medicinal value of this compound.

关 键 词：脱氢弯孢霉菌素 α β不饱和双键 肝微粒体代谢 

分 类 号：R969.1[医药卫生—药理学]