[BMIM]BF4 Mediated Multi-component Synthesis of Phenyl-4-(1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]quinolin-5(4H)-ones and Evaluation of their Anti-cancer Activity

Abstract

Pyrazolo bridged quinolones scaffolds are an important building block in many of the medicinally active new chemical entities. In the current work, synthesis of phenyl-4-(1H-pyrazol-5-yl) conjugated with 1H-pyrazolo[3,4-b]quinolin-5(4H)-ones derivatives has been achieved by one-pot three-component reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine 1, 5,5-dimethylcyclohexane-1,3-diones 2, and 1H-pyrazole-5-carbaldehydes 3 using [BMIM]BF4 as green reaction medium with good yields. Furthermore, the synthesized compounds were evaluated for cytotoxic potential towards HeLa and DU145 cells. Of the eight derivatives, compound 4d exhibited good cytotoxicity with an IC50 value of 8.5 and 8.9 µM against DU145 and HeLa cells, respectively. The molecular docking studies revealed that compound 4d displayed good binding energy (-8.4 kcal/mol) against human checkpoint kinase 1.