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

Masaharu Sakamoto; Seriha Kai; Hiroshi Tateishi; Tanima Biswas; Takashi Sakamoto; Misaki Teshima; Misaki Iwanaga; Akiko Nishikawa; Arisa Sakamoto; Rie Shimozono; Hiroki Kameyama; Masami Nambu; Takuya Masunaga; Kensaku Anraku; Mikako Fujita; Masami Otsuka

doi:10.1055/a-2500-9552

Synlett, Inhaltsverzeichnis

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

Autor*innen

Masaharu Sakamoto‡

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
Seriha Kai‡

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
Hiroshi Tateishi‡

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

^bResearch & Development, Hirata Corporation, Kumamoto, Kumamoto, Japan
Tanima Biswas

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
Takashi Sakamoto

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
Misaki Teshima

^cDepartment of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan
Misaki Iwanaga

^cDepartment of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan
Akiko Nishikawa

^cDepartment of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan
Arisa Sakamoto

^cDepartment of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan
Rie Shimozono

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
Hiroki Kameyama

^cDepartment of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan
Masami Nambu

^cDepartment of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan
Takuya Masunaga

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
Kensaku Anraku

^cDepartment of Medical Technology, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan
Mikako Fujita∗

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
Masami Otsuka∗

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

^dScience Farm Ltd., Kumamoto, Kumamoto, Japan

Abstract

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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

Volltext

Referenzen

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Zusatzmaterial

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