Synthesis and biological evaluation of novel 1-O- and 14-O-derivatives of oridonin as potential anticancer drug candidates.
Novel 1-O- and 14-O-derivatives of oridonin were synthesized and biologically evaluated. All of the derivatives exhibited stronger cytotoxicity against six cancer cell lines (BGC-7901, SW-480, HL-60, BEL-7402, A549, and B16) than oridonin in vitro, and some of them were more potent than oridonin and cyclophosphamide in vivo. Compounds Ib and IIg were the most potent with the IC(50) values of 0.84 microM for Ib in HL-60 cell and 1.00 microM for IIg in BEL-7402 cell.
Xu
Jinyi
J
Department of Medicinal Chemistry, China Pharmaceutical University, Tongjia Xiang 24, Nanjing 210009, China. jinyixu@china.com
Yang
Jingyi
J
Ran
Qian
Q
Wang
Lei
L
Liu
Jie
J
Wang
Zhixuan
Z
Wu
Xiaoming
X
Hua
Weiyi
W
Yuan
Shengtao
S
Zhang
Luyong
L
Shen
Mingqin
M
Ding
Yongfang
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000302:isolation & purification*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000138:chemical synthesis / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D013778:Tetrazolium Salts; D013844:Thiazoles; C011959:oridonin; C022616:thiazolyl blue; D005472:Fluorouracil