Targeting prostate cancer via therapeutic targeting of PIM-1 kinase by Naringenin and Quercetin

PIM-1 kinase belongs to the Ser/Thr kinases family, an attractive therapeutic target for prostate cancer. Here, we screened about 100 natural substances to find potential PIM-1 inhibitors. Two natural compounds, Naringenin and Quercetin, were finally selected based on their PIM-1 inhibitory potential and binding affinities. The docking score of Naringenin and Quercetin with PIM-1 is −8.4 and − 8.1 kcal/mol, respectively. Fluorescence binding studies revealed a strong affinity (Ka values, 3.1 × 104 M−1 and 4.6 × 107 M−1 for Naringenin and Quercetin, respectively) with excellent IC50 values for Naringenin and Quercetin (28.6 μM and 34.9 μM, respectively). Both compounds inhibited the growth of prostate cancer cells (LNCaP) in a dose-dependent manner, with the IC50 value of Naringenin at 17.5 μM and Quercetin at 8.88 μM. To obtain deeper insights into the PIM-1 inhibitory effect of Naringenin and Quercetin, we performed extensive molecular dynamics simulation studies, which provided insights into the binding mechanisms of PIM-1 inhibitors. Finally, Naringenin and Quercetin were suggested to serve as potent PIM-1 inhibitors, offering targeted treatments of prostate cancer. In addition, our findings may help to design novel Naringenin and Quercetin derivatives that could be effective in therapeutic targeting of prostate cancer. •PIM-1 is an attractive drug target for prostate cancer therapy.•We have discovered Naringenin and Quercetin as potent PIM-1 kinase inhibitors.•Docking and MD simulation studies suggested a strong binding and the formation of stable protein-ligands complexes.•Naringenin and Quercetin significantly inhibit the activity of PIM-1 with excellent IC50 values.•Both compounds show cytotoxic effect on LNCaP cells with admirable IC50 values.