2. Academic Validation
  3. Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B

Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B

  • ACS Med Chem Lett. 2011 Mar 4;2(5):348-52. doi: 10.1021/ml100287y.
Naoko Yasobu 1,  Mariko Kitajima 1,  Noriyuki Kogure 1,  Yoshiyuki Shishido 2,  Takeshi Matsuzaki 2,  Masato Nagaoka 2,  Hiromitsu Takayama 1
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Chiba University.
  • 2 Yakult Central Institute for Microbiological Research.
PMID: 24900316 DOI: 10.1021/ml100287y
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.

Keywords

Alkaloid; bioactivity; cathepsin B; colchicine; pro-drug; structure modification.

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