Flexible Analogues of Azaindole DYRK1A Inhibitors Elicit Cytotoxicity in Glioblastoma Cells*

Qingqing Zhou; Tristan A. Reekie; Ramzi H. Abbassi; Dinesh Indurthi Venkata; Josep S. Font; Renae M. Ryan; Louis M. Rendina; Lenka Munoz; Michael Kassiou

doi:10.1071/CH18251

RESEARCH ARTICLE

Flexible Analogues of Azaindole DYRK1A Inhibitors Elicit Cytotoxicity in Glioblastoma Cells*

Qingqing Zhou ^A , Tristan A. Reekie ^A , Ramzi H. Abbassi ^B , Dinesh Indurthi Venkata ^B , Josep S. Font ^C , Renae M. Ryan ^C , Louis M. Rendina ^A , Lenka Munoz ^B and Michael Kassiou ^A ^D

+ Author Affiliations

- Author Affiliations

^A School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

^B School of Medical Sciences, Discipline of Pathology and Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.

^C School of Medical Sciences, Discipline of Pharmacology, The University of Sydney, Sydney, NSW 2006, Australia.

^D Corresponding author. Email: michael.kassiou@sydney.edu.au

Australian Journal of Chemistry 71(10) 789-797 https://doi.org/10.1071/CH18251
Submitted: 28 May 2018 Accepted: 26 June 2018 Published: 30 July 2018

Abstract

DYRK1A is a novel target for epidermal growth factor receptor (EGFR)-dependent glioblastoma and it represents a promising strategy for cancer therapy. DYRK1A inhibition has been found to promote EGFR degradation in glioblastoma cells by triggering endocytosis and lysosomal degradation, thus reducing the self-renewal ability of tumorigenic cells. Using a deconstruction approach of a DYRK1A lead molecule DANDY (1a), a set of novel ring-opened compounds was prepared. Despite showing no activity towards DYRK1A, a reduction in the viability of glioblastoma cells was observed with some of the compounds. This suggests other mechanistic pathways are leading to the apoptosis of glioblastoma cells.

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