title: A Dual Non-ATP Analogue Inhibitor of Aurora Kinases A and B, Derived from Resorcinol with a Mixed Mode of Inhibition.
abstract: 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 (PTK66), a dual inhibitor of Aurora A and Aurora B kinases. PTK66 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 IC50 is approximately 47 and 40 μm for Aurora A and Aurora B kinases, respectively. In cellular systems, PTK66 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.
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.
authors.forename: Dhanasekaran
authors.initials: D
authors.lastname: Karthigeyan
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.
authors.forename: Sudhevan
authors.initials: S
authors.lastname: Surabhi
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.
authors.forename: Pushpak
authors.initials: P
authors.lastname: Mizar
authors.affiliation: Light Scattering Laboratory, Chemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.
authors.forename: Siddhanta
authors.initials: S
authors.lastname: Soumik
authors.affiliation: Biophysics & Strucural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidar Nagar, Kolkata, 700 064, West Bengal, India.
authors.forename: Amrita
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.
authors.forename: Sarmistha Halder
authors.initials: SH
authors.lastname: Sinha
authors.affiliation: Biophysics & Strucural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidar Nagar, Kolkata, 700 064, West Bengal, India.
authors.forename: Dipak
authors.initials: D
authors.lastname: Dasgupta
authors.affiliation: Light Scattering Laboratory, Chemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.
authors.forename: Chandrabhas
authors.initials: C
authors.lastname: Narayana
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D012118:Resorcinols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D012118:Resorcinols; D000255:Adenosine Triphosphate; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; C031389:resorcinol
keywords: Aurora kinase; PTK66; non-ATP analogue inhibitor; surface-enhanced Raman spectroscopy