Cytotoxic biotransformed products from triptonide by Aspergillus niger.
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 5alpha-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 IC (50) values were 5-15 fold less than 1, while 2 is about 100 times less active than 1.
The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100-083, P.R. China.
Lili
L
Ning
Guiqin
G
Qu
Min
M
Ye
Hongzhu
H
Guo
Kaishun
K
Bi
Dean
D
Guo
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001234:Aspergillus niger; D001711:Biotransformation; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014315:Triterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D014315:Triterpenes; C084079:triptonide