Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

0493391 - ÚOCHB 2019 RIV GB eng J - Článek v odborném periodiku
Vekariya, M. K. - Vekariya, R. H. - Brahmkshatriya, Pathik - Shah, N. K.
Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation.
Chemical Biology & Drug Design. Roč. 92, č. 3 (2018), s. 1683-1691. ISSN 1747-0277. E-ISSN 1747-0285
Institucionální podpora: RVO:61388963
Klíčová slova: cyclin-dependent kinase 2 * docking * pyrazole * structure-based design
Obor OECD: Physical chemistry
Impakt faktor: 2.256, rok: 2018

A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50<20nm), which can be further optimized to have selectivity over other kinase isoforms.
Trvalý link: http://hdl.handle.net/11104/0286748