Synthesis, antibacterial and cytotoxic evaluation of flavipucine and its derivatives

Yasuha Kusakabe; Shoma Mizutani; Shogo Kamo; Tatsuki Yoshimoto; Shusuke Tomoshige; Tsuneomi Kawasaki; Ryoko Takasawa; Kazunori Tsubaki; Kouji Kuramochi

doi:10.1016/j.bmcl.2019.03.034

Synthesis, antibacterial and cytotoxic evaluation of flavipucine and its derivatives

Bioorg Med Chem Lett. 2019 Jun 1;29(11):1390-1394. doi: 10.1016/j.bmcl.2019.03.034. Epub 2019 Mar 26.

Authors

Yasuha Kusakabe¹, Shoma Mizutani², Shogo Kamo³, Tatsuki Yoshimoto¹, Shusuke Tomoshige¹, Tsuneomi Kawasaki⁴, Ryoko Takasawa⁵, Kazunori Tsubaki², Kouji Kuramochi⁶

Affiliations

¹ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
² Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan.
³ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan.
⁴ Department of Applied Chemistry, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
⁵ Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
⁶ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: kuramoch@rs.tus.ac.jp.

PMID: 30935798
DOI: 10.1016/j.bmcl.2019.03.034

Abstract

The antibacterial and cytotoxic activity of seven racemic lactams and both enantiomers of flavipucine were evaluated. Of the compounds tested in this study, flavipucine and phenylflavipucine displayed bactericidal activity against Bacillus subtilis. These results indicate that the pyridione epoxide moiety is a pharmacophore for antibacterial activity against B. subtilis. Flavipucine showed cytotoxic activity against several cancer cells. The cytotoxic activity of flavipucine against human leukemia HL-60 cells is as strong as that of SN-38, the active metabolite of irinotecan. In contrast, the cytotoxic activity of flavipucine against nonneoplastic HEK293 cells and human normal MRC-5 cells is weaker than that of SN-38. No significant differences in the biological activity of the racemates or enantiomers of flavipucine were observed.

Keywords: Antibacterial activity; Cytotoxicity; Lactam; Natural product.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Bacillus subtilis / drug effects*
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Escherichia coli / drug effects*
Humans
Microbial Sensitivity Tests
Molecular Structure
Pyridones / chemical synthesis
Pyridones / chemistry
Pyridones / pharmacology
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Antineoplastic Agents
Pyridones
flavipucine