Preparation of yuanhuacine and relative daphne diterpene esters from Daphne genkwa and structure-activity relationship of potent inhibitory activity against DNA topoisomerase I.
Two new daphne diterpene esters Yuanhuajine (2) and Yuanhuagine (4), together with three known daphne diterpene esters yuanhuacine (1), yuanhuadine (3), and yuanhuapine (5), were isolated and identified from Daphne genkwa, a traditional Chinese medicine. Their structures were elucidated by a combination of UV, IR, MS and NMR ((1)H NMR, (13)C NMR, HSQC, and HMBC) spectra. In order to explore the structure-activity relationship, three compounds 6, 7, and 8 were prepared as three derivatives of 1. Inhibitory activities against DNA topoisomerase I (topo I) were assessed for the compounds 1-8. These compounds, except for 8, exhibited potent inhibitory activities against DNA topo I at IC(50) levels of 11.1-53.4 microM and they are new type of topo I inhibitors bearing different structures compared with the known topo I inhibitors. The agarose-gel electrophoresis experiments showed that the orthoester group of daphne diterpene esters was necessary for the inhibitory activity against DNA topo I, and the inhibition against DNA topo I is probably one of the anti-tumor mechanisms of daphne diterpene esters.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Zhongshan Road 158-90, Dalian 116012, China. zsx56@yahoo.com.cn
Shixuan
S
Zhang
Xiaona
X
Li
Fenghong
F
Zhang
Puwen
P
Yang
Xiujuan
X
Gao
Qiling
Q
Song
D032364:Daphne / Q000737:chemistry*; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008518:Medicine, East Asian Traditional; D008968:Molecular Conformation; D018517:Plant Roots / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry; D059004:Topoisomerase I Inhibitors
D004224:Diterpenes; D004791:Enzyme Inhibitors; D004952:Esters; D013729:Terpenes; D059004:Topoisomerase I Inhibitors; C512332:Yuanhuagine; C512329:Yuanhuajine; C512330:Yuanhuapine; C029912:Yuanhuacin; C039652:yuanhuadine