Synthesis and biological evaluation of novel triptolide analogues for anticancer activity.
Three types of novel triptolide analogues with 9,11-olefin (3-5), five-membered unsaturated lactam ring (6-7) or A/B cis ring junction (8-14) were synthesized. Although with 9,11-olefin instead of 9,11-β-epoxide, compound 4a was much more active than the parent natural triptolide (1) with the lowest IC(50) value of 0.05nM for SKOV-3 cells, clearly challenging the traditional viewpoint on the necessity of 9,11-β-epoxide group of triptolide. In addition, structure-activity relationships for three classes of compounds were studied.
Zhou
Bing
B
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Road Zu Chong Zhi, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
Miao
Zehong
Z
Deng
Gang
G
Ding
Jian
J
Yang
Yaxi
Y
Feng
Huijin
H
Li
Yuanchao
Y
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D029757:Tripterygium / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D004852:Epoxy Compounds; D007202:Indicators and Reagents; D010616:Phenanthrenes; C001899:triptolide