Design and synthesis of new pyrazolylbenzimidazoles as sphingosine kinase-1 inhibitors

Sphingosine-1 kinase (SphK1) is one of the important enzymes phospholipids and its inhibition therapeutic strategies for different diseases. SphK1 over expression observed in types cancer indicating role tumor growth. In search effective inhibitors, a new series pyrazolylbenzimidazoles was synthesized evaluated as sphingosine kinase-1 inhibitors. order to evaluate binding affinities all compounds, compounds were subjected docking analysis fluorescence quenching. The results indicated that there consistency between quenching results, which revealed 47 48 exhibited significant decrease intensity well they formed stable protein–ligand complexes. addition, enzyme assay performed showed inhibitory potential toward SphK1. Moreover, IC50 values displayed most promising compounds. antiproliferation study against NCI-60 cell line panel. target demonstrated antitumor activity growth lines. Most these fit into ATP-binding site form hydrogen-bonding interactions with catalytically relevant residues predicted by molecular docking. this article, insight has been given importance inhibitors perspectives hold future research.