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A Dual Non‐ ATP Analogue Inhibitor of Aurora Kinases A and B, Derived from Resorcinol with a Mixed Mode of Inhibition
Author(s) -
Karthigeyan Dhanasekaran,
Surabhi Sudhevan,
Mizar Pushpak,
Soumik Siddhanta,
Banerjee Amrita,
Sinha Sarmistha Halder,
Dasgupta Dipak,
Narayana Chandrabhas,
Kundu Tapas K.
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12728
Subject(s) - kinase , aurora inhibitor , aurora b kinase , chemistry , polo like kinase , aurora kinase , protein serine threonine kinases , phosphorylation , resorcinol , biochemistry , microbiology and biotechnology , protein kinase a , biology , cell cycle , cell , cytokinesis , cell division , organic chemistry
Aurora kinases are the most commonly targeted mitotic kinases in the intervention of cancer progression. Here, we report a resorcinol derivative, 5‐methyl‐4‐(2‐thiazolylazo) resorcinol ( PTK 66), a dual inhibitor of Aurora A and Aurora B kinases. PTK 66 is a surface binding non‐ ATP analogue inhibitor that shows a mixed pattern of inhibition against both of Aurora A and B kinases. The in vitro IC 50 is approximately 47 and 40 μ m for Aurora A and Aurora B kinases, respectively. In cellular systems, PTK 66 exhibits a substantially low cytotoxicity at micromolar concentrations but it can induce aneuploidy under similar dosages as a consequence of Aurora kinase inhibition. This result was corroborated by a drop in the histone H3 (S10) phosphorylation level detected via Western blot analysis using three different cell types. Altogether, our findings indicate that the ligand containing resorcinol backbone is one of the novel scaffolds targeting the Aurora family of kinases, which could be a target for antineoplastic drug development.