Biotransformation of malabaricone C by rat hepatic microsomes and cytotoxic activities against gastric cancer cells in vitro

doi:10.5246/jcps.2014.04.033

Journal of Chinese Pharmaceutical Sciences ›› 2014, Vol. 23 ›› Issue (4): 241-245.DOI: 10.5246/jcps.2014.04.033

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Biotransformation of malabaricone C by rat hepatic microsomes and cytotoxic activities against gastric cancer cells in vitro

Ni Wu, Wei Xu, Youbo Zhang, Xiuwei Yang^*

State Key Laboratory of Natural and Biomimetic Drugs; Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2013-12-19 Revised:2014-01-26 Online:2014-04-28 Published:2014-02-13
Contact: *Corresponding author. Tel.: 86-10-82801569; E-mail: xwyang@bjmu.edu.cn
About author:*Corresponding author. Tel.: 86-10-82801569; E-mail: xwyang@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 30973863; 81161120429) and National Key Technology R & D Program of China (Grant No. 2011BAI07B08).

Abstract

Abstract:

Malabaricone C (1), isolated from the seeds of Myristica fragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investigated using rat hepatic microsomes for the first time and the main biotransformation product waselucidated as malabaricone B (2) according to the spectroscopic data. Further evaluation on human gastric cancer cell lines showed that the cytotoxic effects of malabaricone C and its metabolite malabaricone B were comparable to those of vinorelbine, with the values of IC₅₀ of (42.62±3.10) and (19.80±1.70) μg/mL on NCI-N87, and (22.94±1.33) and (19.60±2.21) μg/mL on MGC803, respectively. Statistical analysis revealed that malabaricone B had significantly stronger cytotoxicity than the parent compound(P<0.01 on NCI-N87 and P<0.05 on MGC803), which may indicate a bioactivation of malabaricone C by hepatic microsomes. These results suggest that malabaricone C has a simple biotransformation pathway by hepatic microsomes and provide valuable information for further investigation on both the parent compound and its biotransformation product as anti-gastric cancer agents or lead compounds.

Key words: Malabaricone C, Malabaricone B, Myristica fragrans, Biotransformation, Rat hepatic microsomes, Human gastric cancer NCI-N87, Human gastric cancer MGC803

CLC Number:

R284

Supporting:

Ni Wu, Wei Xu, Youbo Zhang, Xiuwei Yang. Biotransformation of malabaricone C by rat hepatic microsomes and cytotoxic activities against gastric cancer cells in vitro[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(4): 241-245.

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Biotransformation of malabaricone C by rat hepatic microsomes and cytotoxic activities against gastric cancer cells in vitro

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