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Synlett 2025; 36(17): 2915-2919
DOI: 10.1055/a-2500-9552
letter
Small Molecules in Medicinal Chemistry

Oxaprozin and SB-431542 Hybrid Molecule Inhibits Fibrosis and Cancer Cell Migration

Authors

  • Masaharu Sakamoto‡

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan

  • Seriha Kai‡

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan

  • Hiroshi Tateishi‡

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
    b   Research & Development, Hirata Corporation, Kumamoto, Kumamoto, Japan

  • Tanima Biswas

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan

  • Takashi Sakamoto

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan

  • Misaki Teshima

    c   Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

  • Misaki Iwanaga

    c   Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

  • Akiko Nishikawa

    c   Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

  • Arisa Sakamoto

    c   Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

  • Rie Shimozono

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan

  • Hiroki Kameyama

    c   Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

  • Masami Nambu

    c   Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

  • Takuya Masunaga

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan

  • Kensaku Anraku

    c   Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

  • Mikako Fujita∗

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan

  • Masami Otsuka∗

    a   Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
    d   Science Farm Ltd., Kumamoto, Kumamoto, Japan

This work was supported by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (17H03999) (to M. O.) and a grant for the Joint Research Project with Science Farm Ltd.
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Abstract

In this study, we synthesized a novel oxaprozin and SB-431542 hybrid molecule, AF-3, exhibiting antifibrotic and anti-cell-migration activities. Although oxaprozin was expected to exhibit antifibrotic activity, this was not observed in this study. Therefore, we designed AF-3 as an oxaprozin derivative and obtained its synthetic precursor, AF-2. Carboxylic acid AF-2 and carboxamide AF-3 showed similar inhibitory activities against AKT phosphorylation and expression of the mesenchymal cell marker, vimentin. Notably, AF-2 exerted weaker effects on cell migration and fibrosis than AF-3. Although the underlying mechanisms remain elusive, this study provides valuable insights for the development of new drugs against fibrosis and cancer metastasis related to cell migration.

Key words

oxaprozin - SB-431542 - hybrid molecule - anti-fibrotic activity - anti-cell migration activity - vimentin - AKT

Supporting Information



Publikationsverlauf

Eingereicht: 13. Oktober 2024

Angenommen nach Revision: 11. Dezember 2024

Accepted Manuscript online:
11. Dezember 2024

Artikel online veröffentlicht:
21. Januar 2025

© 2025. Thieme. All rights reserved

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