New insight into the bioactivity of substituted benzimidazole derivatives: Repurposing from anti-HIV activity to cell migration inhibition targeting hnRNP M.

Mohamed O Radwan, Tsugumasa Toma, Yuiichi Arakaki, Masahiro Kamo, Naoya Inoue, Ryoko Koga, Masami Otsuka, Hiroshi Tateishi, Mikako Fujita

Bioorganic & medicinal chemistry 2023 May 15

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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. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Mohamed O Radwan, Tsugumasa Toma, Yuiichi Arakaki, Masahiro Kamo, Naoya Inoue, Ryoko Koga, Masami Otsuka, Hiroshi Tateishi, Mikako Fujita. New insight into the bioactivity of substituted benzimidazole derivatives: Repurposing from anti-HIV activity to cell migration inhibition targeting hnRNP M. Bioorganic & medicinal chemistry. 2023 May 15;86:117294