Oxaprozin and SB-431542 Hybrid Molecule Inhibits Fibrosis and Cancer Cell Migration
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.
Authors
- Hiroki Kameyama (ORCID: https://orcid.org/0000-0002-4847-8244)
- Mikako Fujita (ORCID: https://orcid.org/0000-0001-6705-4052)
- Misaki Iwanaga (ORCID: https://orcid.org/0000-0002-5259-4790)
- Tanima Biswas
- Arisa Sakamoto
- Hiroshi Tateishi (ORCID: https://orcid.org/0000-0003-1225-0720)
- Rie Shimozono
- Takashi Sakamoto (ORCID: https://orcid.org/0000-0001-5272-7517)
- Takuya Masunaga (ORCID: https://orcid.org/0000-0002-5774-3820)
- Masami Otsuka (ORCID: https://orcid.org/0000-0002-2968-3939)
- Masami Nambu
- Masaharu Sakamoto
- Seriha Kai
- Masanori Teshima (ORCID: https://orcid.org/0000-0002-4409-0525)
- Akiko Nishikawa
- Kensaku Anraku
Institutions
- Kumamoto Health Science University (JP)
- Farm Foundation (US)
- ARCH Development Corporation (US)
- For farmers (United Kingdom) (GB)
- Murata (Japan) (JP)
- Kumamoto University (JP)
Publication Details
- Journal
- Synlett
- Published
- 2024-12-11
- DOI
- https://doi.org/10.1055/a-2500-9552
- Citations
- 1
- Primary Topic
- Synthesis and Biological Evaluation
- Type
- article
- Field-Weighted Citation Impact
- 0.25
Funders
- Japan Society for the Promotion of Science