Liver microsomal metabolism of dehydrocurvularin， an ACLY inhibitor
ZHOU Fugui 1， LI Yulan 2， CAI Xiaorong 3， XUE Lian 4， DENG Zhangshuang 1
(1.Hubei Key Laboratory of Natural Products Research and Development， College of Biological and Pharmaceutical Sciences， China Three Gorges University， Yichang 443002， Hubei， China； 2. The First Clinical Medical College of China Three Gorges University， Yichang Center People's Hospital， Yichang 443003， Hubei， China； 3. Three Gorges Public Inspection and Testing Center， Yichang 443000， Hubei， China； 4. HEC API Yichang Co.，Ltd.， Yichang 443311， Hubei， China)
Abstract：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 the α，β unsaturated 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.
2022, Vol. 56 
