title: Synthesis and cytotoxicity of racemic isodeoxypodophyllotoxin analogues with isoprene-derived side chains.
abstract: 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).
authors.affiliation: 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
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ju Hong
authors.initials: JH
authors.lastname: Feng
authors.forename: Hong Xia
authors.initials: HX
authors.lastname: Ding
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiong
authors.forename: Christopher H K
authors.initials: CH
authors.lastname: Cheng
authors.forename: Xiao Jiang
authors.initials: XJ
authors.lastname: Hao
authors.forename: Yong Min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Yuan Jiang
authors.initials: YJ
authors.lastname: Pan
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéritte
authors.forename: Xiu Mei
authors.initials: XM
authors.lastname: Wu
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Joachim
authors.initials: J
authors.lastname: Stöckigt
mesh_terms: 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
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene; D011034:Podophyllotoxin