title: Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B.
abstract: Novel colchicine derivatives possessing various substituents at the C4 position were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher activity against cancer cell lines (A549, HT29, HCT116) as well as on mice transplanted with the HCT116 human colorectal carcinoma cell line than colchicine (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs having a dipeptide side chain and demonstrated that these pro-drugs were activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited selective toxicity to the tumor cells.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yasobu
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kitajima
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kogure
authors.affiliation: Yakult Central Institute for Microbiological Research.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shishido
authors.affiliation: Yakult Central Institute for Microbiological Research.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Yakult Central Institute for Microbiological Research.
authors.forename: Masato
authors.initials: M
authors.lastname: Nagaoka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takayama
keywords: Alkaloid; bioactivity; cathepsin B; colchicine; pro-drug; structure modification