title: Design, synthesis and potent cytotoxic activity of novel podophyllotoxin derivatives.
abstract: Twenty new acyl thiourea derivatives of podophyllotoxin and 4'-demethylepipodophyllotoxin were prepared and screened for their cytotoxicity against four human tumor cell lines, A-549, DU-145, KB, and KBvin. With IC50 values of 0.098-1.13 μM, compounds 13b, 13c, and 13o displayed much better cytotoxic activity than the control etoposide. Most importantly, 13b and 13o exhibited promising cytotoxicity against the drug resistant tumor cell line KBvin with IC50 values of 0.098 and 0.13 μM, respectively, while etoposide lost activity completely. Structure-activity relationship (SAR) correlations of the new derivatives have been established. Compounds 13b and 13o merit further development as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidates.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Wen-Qun
authors.initials: WQ
authors.lastname: Li
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xu-Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Keduo
authors.initials: K
authors.lastname: Qian
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: khlee@email.unc.edu.
authors.forename: Ying-Qian
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Chih-Ya
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Environmental and Municipal Engineering School, Lanzhou Jiaotong University, Lanzhou 730000, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Tian
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xing-Wen
authors.initials: XW
authors.lastname: Zhou
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan. Electronic address: yqliu@lzu.edu.cn.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007624:KB Cells; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D013890:Thiourea; D011034:Podophyllotoxin