Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A. Issue 22 (1st December 2018)

• Record Type: Journal Article
• Authors: Zhou, Qingqing; Reekie, Tristan A.; Abbassi, Ramzi H.; Indurthi Venkata, Dinesh; Font, Josep S.; Ryan, Renae M.; Munoz, Lenka; Kassiou, Michael
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 22(2018)
• Page Start: 5852
• Page End: 5869
• Publication Date: 2018-12-01
• Subjects: Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.10.034
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.