| RRC ID |
74909
|
| 著者 |
Radwan MO, Toma T, Arakaki Y, Kamo M, Inoue N, Koga R, Otsuka M, Tateishi H, Fujita M.
|
| タイトル |
New insight into the bioactivity of substituted benzimidazole derivatives: Repurposing from anti-HIV activity to cell migration inhibition targeting hnRNP M.
|
| ジャーナル |
Bioorg Med Chem
|
| Abstract |
Drug repurposing is a distinguished approach for drug development that saves a great deal of time and money. Based on our previous successful repurposing of a compound BMMP from anti-HIV-1 therapy to anti-cancer metastatic activity, we adopted the same techniques for repurposing benzimidazole derivatives considering MM-1 as a lead compound. An extensive structure-activity relationship (SAR) study afforded three promising compounds, MM-1d, MM-1h, and MM-1j, which inhibited cell migration in a similar fashion to BMMP. These compounds suppressed CD44 mRNA expression, whereas only MM-1h further suppressed mRNA expression of the epithelial-mesenchymal transition (EMT) marker zeb 1. Using benzimidazole instead of methyl pyrimidine as in BMMP resulted in better affinity for heterogeneous nuclear ribonucleoprotein (hnRNP) M protein and higher anti-cell migration activity. In conclusion, our study identified new agents that surpass the affinity of BMMP for hnRNP M and have anti-EMT activity, which makes them worthy of future attention and optimization.
|
| 巻・号 |
86
|
| ページ |
117294
|
| 公開日 |
2023-4-25
|
| DOI |
10.1016/j.bmc.2023.117294
|
| PII |
S0968-0896(23)00142-6
|
| PMID |
37141680
|
| MeSH |
Cell Line, Tumor
Cell Migration Inhibition
Drug Repositioning*
Heterogeneous-Nuclear Ribonucleoprotein Group M*
RNA, Messenger / genetics
|
| IF |
3.073
|
| リソース情報 |
| ヒト・動物細胞 |
A549 |
