From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase

Significant inhibition of Aurora B was achieved by the synthesis simplified fragments benzosceptrins and oroidin belonging to marine pyrrole-2-aminoimidazoles metabolites isolated from sponges. Evaluation kinase enabled discovery a synthetically accessible rigid acetylenic structural analogue EL-228 (1), whose structure could be optimized into potent CJ2-150 (37). Here we present new inhibitors kinase, which is an important target for cancer therapy through mitosis regulation. The biologically oriented yielded several nanomolar inhibitors. compound (37) showed non-ATP competitive allosteric mode action in mixed-type kinase. Molecular docking identified probable binding site “F” highlighted key interactions with protein. We describe improvement inhibitory potency specificity novel scaffold as well characterization mechanism action.