1. Targeting prostate cancer via therapeutic targeting of PIM-1 kinase by Naringenin and Quercetin.
- Author
-
Rathi, Aanchal, Chaudhury, Arunabh, Anjum, Farah, Ahmad, Shahbaz, Haider, Shaista, Khan, Zeba Firdos, Taiyab, Aaliya, Chakrabarty, Anindita, Islam, Asimul, Hassan, Md. Imtaiyaz, and Haque, Mohammad Mahfuzul
- Subjects
- *
CANCER cell growth , *MOLECULAR dynamics , *DRUG target , *DRUG design , *PROSTATE cancer , *QUERCETIN - Abstract
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 (K a values, 3.1 × 104 M−1 and 4.6 × 107 M−1 for Naringenin and Quercetin, respectively) with excellent IC 50 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 IC 50 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 IC 50 values. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF