2. Academic Validation
  3. Structure-activity relationship study of syringolin A as a potential anticancer agent

Structure-activity relationship study of syringolin A as a potential anticancer agent

  • Bioorg Med Chem Lett. 2015 Nov 1;25(21):4872-4877. doi: 10.1016/j.bmcl.2015.06.015.
Takuya Chiba 1,  Akira Matsuda 2,  Satoshi Ichikawa 3
Affiliations

Affiliations

  • 1 Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • 2 Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
  • 3 Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: ichikawa@pharm.hokudai.ac.jp.
PMID: 26231162 DOI: 10.1016/j.bmcl.2015.06.015
Abstract

A detailed structure-activity relationship of syringolin A (1), which is a promising antitumor natural product, was described. We previously developed syringolin A analog 2 as a potent Proteasome Inhibitor by the structure-based drug design of syringolin A. In this Letter, we synthesized a range of analogs of 2, having a different length of the lipophilic chain and substituted aryl group, and their cytotoxicity against human Cancer cells was evaluated. It turned out that these modifications greatly affected the cytotoxicity. Further optimization would lead to develop a novel Proteasome Inhibitor.

Keywords

Cancer; Proteasome inhibitor; Structure–activity relationship.

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