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

鞘氨醇 1 激酶 (SphK1) 是磷脂的重要酶之一，其抑制是不同疾病的治疗策略之一。在不同类型的癌症中观察到 SphK1 过表达，表明其在肿瘤生长中的重要作用。为了寻找有效的 SphK1 抑制剂，合成了一系列新的吡唑基苯并咪唑并作为鞘氨醇激酶-1 (SphK1) 抑制剂进行了评估。为了评估所有合成化合物的结合亲和力，对所有化合物进行对接分析和荧光猝灭。结果表明，对接和荧光猝灭结果具有一致性，表明化合物47和48SphK1 的荧光强度显着降低，并形成稳定的蛋白质-配体复合物。此外，还进行了酶抑制试验，显示出对 SphK1 的有效抑制潜力。此外，IC ₅₀值显示化合物47和48是最有希望的化合物。此外，针对 NCI-60 细胞系面板对所有合成化合物进行了抗增殖研究。目标化合物47和48证明了对癌细胞系的有效抗肿瘤活性和生长抑制潜力。大多数这些化合物都非常适合 SphK1 的 ATP 结合位点，并与分子对接预测的催化相关残基形成显着的氢键相互作用。在本文中，深入了解了吡唑基苯并咪唑作为 SphK1 抑制剂的重要性以及它们对未来研究的展望。