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
› Author Affiliations
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.


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



Publication History

Received: 13 October 2024

Accepted after revision: 11 December 2024

Accepted Manuscript online:
11 December 2024

Article published online:
21 January 2025

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