Synthesis and cytotoxicity of racemic isodeoxypodophyllotoxin analogues with isoprene-derived side chains.
A series of isodeoxypodophyllotoxin (5) analogues, 26-38, with various isoprene-derived side chains at the E-ring were designed and synthesized. For comparison, compound 39, with a benzyloxy group on the E-ring, and six D-ring opened analogues, 40-45, were also prepared. All the synthetic compounds were evaluated for their cytotoxic activities in vitro against seven cultured human tumor cell lines. Compounds 27, 43, and 44 were more cytotoxic than etoposide on BEL-7404, A549, and HL-60 cell lines, respectively. However, none of the synthetic isodeoxypodophyllotoxins were more cytotoxic than podophyllotoxin (1).
Zhao
Yu
Y
Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Yan An Road 353, Hangzhou 310031, People's Republic of China. dryuzhao@zju.edu.cn
Feng
Ju Hong
JH
Ding
Hong Xia
HX
Xiong
Yi
Y
Cheng
Christopher H K
CH
Hao
Xiao Jiang
XJ
Zhang
Yong Min
YM
Pan
Yuan Jiang
YJ
Guéritte
Françoise
F
Wu
Xiu Mei
XM
Bai
Hua
H
Stöckigt
Joachim
J
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002070:Butadienes / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D045782:Hemiterpenes / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010420:Pentanes / Q000737:chemistry*; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene; D011034:Podophyllotoxin