Synlett
DOI: 10.1055/a-2500-9552
letter
Small Molecules in Medicinal Chemistry

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

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
› Institutsangaben

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.


Preview

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.

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

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany