Multiple myeloma (MM) is a devastating disease with low survival rates worldwide. The mean lifetime of patients may be extendable with new
drug alternatives.
Aurora A kinase (
AURKA) is crucial in
oncogenesis, because its overexpression or amplification may incline the development of various types of
cancer, including MM. Therefore, inhibitors of
AURKA are innovative and promising targets. Natural compounds always represented a valuable resource for anticancer
drug development. In the present study, based on virtual
drug screening of more than 48,000 natural compounds, the
antibiotic deschloro-chlorotricin (DCCT) has been identified to bind to
AURKA with even higher binding affinity (free bindung energy: -12.25 kcal/mol) than the known
AURKA inhibitor,
alisertib (free binding energy: -11.25 kcal/mol). The in silico studies have been verified in vitro by using microscale thermophoresis. DCCT inhibited MM cell lines (KMS-11, L-363, RPMI-8226, MOLP-8, OPM-2, NCI-H929) with IC50 values in a range from 0.01 to 0.12 μM. Furthermore, DCCT downregulated
AURKA protein expression, induced G2/M cell cycle arrest and disturbed the cellular microtubule network as determined by Western blotting, flow cytometry, and fluorescence microscopy. Thus, DCCT may be a promising lead structure for further derivatization and the development of specific
AURKA inhibitors in MM
therapy.