Design, synthesis and biological evaluation of benzimidazole carbamide derivatives – potential autophagy inducers

Two benzimidazole carbamide derivatives exhibited autophagy-inducing activity at concentrations ≥100 μM.

• A benzimidazole derivative without a carbamide fragment showed the most favorable activity-toxicity profile.
• The compounds primarily activate autophagy through the AMPK pathway.
• The derivatives displayed low selectivity toward individual components of the AMPK signaling cascade.
• One specific derivative with a pyridyl substituent and a methylated benzimidazole core preferentially targeted AMPK.
• The synthesized benzimidazoles are considered mild autophagy activators and broad modulators of cellular signaling.

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