4.5 Article

Dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-ones as a new class of CK2 inhibitors

Journal

MOLECULAR DIVERSITY
Volume 22, Issue 4, Pages 991-998

Publisher

SPRINGER
DOI: 10.1007/s11030-018-9836-1

Keywords

CK2 inhibitors; Dihydrobenzo[4,5]imidazo[1, 2-a]pyrimidin-4-one derivatives; Virtual screening; Molecular docking; In vitro biochemical assay

Funding

  1. National Academy of Sciences of Ukraine [10112U004110]

Ask authors/readers for more resources

Identification of new small molecules inhibiting protein kinase CK2 is highly required for the study of this protein's functions in cell and for the further development of novel pharmaceuticals against a variety of disorders associated with CK2 activity. In this article, a virtual screening of a random small-molecule library was performed and 12 compounds were initially selected for biochemical tests toward CK2. Among them, the most active compound 1 (IC50 = 6.8 mu M) belonged to dihydrobenzo[4,5] imidazo[1,2-a] pyrimidine-4-ones. The complex of this compound with CK2 was analyzed, and key ligand-enzyme interactions were determined. Then, a virtual screening of 231 dihydrobenzo[4,5] imidazo[1,2-a] pyrimidine-4-one derivatives was performed and 37 compounds were chosen for in vitro testing. It was found that 32 compounds inhibit CK2 with IC50 values from 2.5 to 7.5 mu M. These results demonstrate that dihydrobenzo[4,5] imidazo[1,2-a] pyrimidine-4-one is a novel class of CK2 inhibitors.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available