Transformation of biindole marine alkaloid FGFC1 by hepatic microsome system
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Received:December 28, 2018  Revised:March 14, 2019
DOI:10.12024/jsou.20181202492
Key Words: liver microsome  FGFC1  biotransformation  half-life  PIO
Author NameAffiliationE-mail
ZHANG Benshuai College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China  
JIANG Shengnan Shanghai Engineering Research Center for Processing and Storage of Seawater Products, Shanghai 201306, China  
YANG Jing Shanghai Engineering Research Center for Processing and Storage of Seawater Products, Shanghai 201306, China  
QIAN Shiyun Shanghai Engineering Research Center for Processing and Storage of Seawater Products, Shanghai 201306, China  
MA Zibin National Freshwater Aquatic Products Processing Technology R & D Center, Shanghai 201306, China  
GUO Ruihua College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China  
BAO Bin College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China  
WU Wenhui College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China whwu@shou.edu.cn 
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Abstract:
      In vitro pharmacokinetics and transformation products of novel marine fibrinolytic compound FGFC1 were studied. Liver microsomes were prepared by Wistar rats. The liver microsome protein concentration was detected by lowry method. The changes of FGFC1 and its transformation products were detected by HPLC method. The conversion products were analyzed by LC-MS/MS method and 4-phenyl-1,2,3-thiadiazole, deacetylcyclopropionate, phenytoin and ketoconazole are selective inhibitors of different subtypes of the CYP450 enzyme system.The in vitro metabolic half-life of FGFC1 was T1/2=(96.25±2.3) min, and the intrinsic clearance rate CLint=(0.072 0±0.001 4) mL/(min·mg).The conversion product of FGFC1 is((2S,3S)-2-((E)-7,8-dihydroxy-4-methylnon-3-en-1-yl)-3,5,8-trihydroxy-2-methyl-3,4,8,9-tetrahydropyrano[2,3-e]isoindol- 7 (2H)-one)(PIO)with a molecular weight of 421.2.The fragments of the FGFC1 conversion product was detected by LC-MS/MS at 463.30[M+C2H3N+H]+ and m/z 110.90[C7H8O+H+H]+, 215.70[C13H26O2+H]+, 337.00[C18H27NO5]+, 337.00[C25H31NO2]+. Phenytoin significantly inhibited the liver microsomal enzyme system CYP3A4 subtype, and the PIO was reduced with 49.11%. FGFC1 is converted by N-dealkylation reaction, N-oxidation reaction and hydrolysis reaction under the catalysis of CYO450 subtype CYP3A4.