Synthesis and cytotoxicity of some new eriocalyxin B derivatives.
Eriocalyxin B (1) was regarded as the promising candidate for new anticancer agent because of its potent activity and novel mechanism of action. Systematic modifications of 1 were done, and nineteen derivatives were synthesized and their cytotoxicities against five tumor cell lines were evaluated. The structure-activity relationship (SAR) of 1 confirmed that the alpha,beta-unsaturated ketone moieties in ring A and D are the leading active sites; the 7,20-epoxy moiety, OH-6 and OH-7 play an important role in keeping the cytotoxicity. The 6,7-seco derivative 19 had remarkable activity while derivative 20 oxidized from 19 was completely inactive, which suggested that the carboxyl group could destroy the cytoxicity of 20 despite the presence of alpha,beta-unsaturated ketone moiety.
Zhao
Yu
Y
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Longquan Road 610, Kunming 650204, Yunnan, People's Republic of China.
Niu
Xue-Mei
XM
Qian
Li-Ping
LP
Liu
Ze-Yuan
ZY
Zhao
Qin-Shi
QS
Sun
Han-Dong
HD
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004224:Diterpenes; C516552:eriocalyxin B