Imidazopyridine-fused [1,3]-diazepinones: Synthesis and antiproliferative activity

• 15 pyrido-imidazodiazepinones were evaluated for their anticancer activities.
• Compound 6a presents a cytotoxic effect on MDA-MB-435 melanoma cells (IC50 = 1.3 μM).
• Compound 6a increased apoptosis in subG1 phase after 48 h treatment.
• Compound 6a significantly inhibited Hepatocyte progenitor kinase-like kinase (HGK).

A series of 15 pyrido-imidazo-1,3-diazepin-5-ones and pyrido-1,3-diazepine-2,5-diones were synthesized and their anticancer activities were evaluated. Among tested compounds on a cell lines panel, compound 6a presents the best growth inhibition activity on 21 cell lines with a cytotoxic effect on MDA-MB-435 melanoma cells. This compound led to deep cell morphological changes and revealed to be an inhibitor of the Hepatocyte progenitor kinase-like kinase (HGK), which is known to be implicated in the migration, adhesion and invasion of various tumor cells.

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