Cytotoxic Biotransformed Products from Triptonide by Aspergillus niger
Lili Ning1, 2
, Guiqin Qu1
, Min Ye1
, Hongzhu Guo1
, Kaishun Bi2
, Dean Guo1
1The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, P. R. China
2Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China
We thank the National Outstanding Youth Foundation by NSF of China (39925040) and Trans-Century Training Program Foundation for the Talents by the Ministry of Education for financial support
The diterpenoid triepoxides are the major active constituents of Tripterygium wilfordii with potent antitumor and immune activities. But the strong toxicity of these compounds has restricted their application to a great extent. In order to find more effective compounds with less toxicity, structural modifications of triptonide (1) by Aspergillus niger (AS 3.739) were investigated and four biotransformed products were obtained. Based on their chemical and spectral data, their structures were elucidated as 5α-hydroxytriptonide (2), triptolide (3), 17-hydroxytriptonide (4), and 16-hydroxytriptonide (5), among which 2, 4 and 5 are new compounds. All the three new transformed products showed cytotoxic activities against the majority of the human tumor cell lines tested, however, they are found to possess less cytotoxic activity when compared with 1. Both compounds 4 and 5 showed similar cytotoxic activity and their IC50 values were 5 - 15 fold less than 1, while 2 is about 100 times less active than 1.
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