Acacetin and pinostrobin as a promising inhibitor of cancer-associated protein kinases

Protein kinases associated with cancer genes play vital role in angiogenesis, invasion, motility, proliferation, and survival. Therefore, cancer prevention/treatment, targeting kinases with phytochemicals could be a promising approach. Given potential of phytochemicals in modulating cancer-associated kinases, present study aims to find inhibitory prospects of selected flavonoids for cancer-chemoprevention/treatment. The molecular docking interaction analysis was done by exploring binding potential of flavonoids with kinases (PI3K, Akt, mTOR, EGFR, MAPK, MKK4, Fyn, ZAP-70, B-Raf, JAK-2, STAT-1, STAT-3, STAT-4, STAT-5, and VEGF) involved in various carcinogenesis phases. Among flavonoids acacetin showed highest binding-energy against JAK-2 following Fyn > VEGF > PI3K > MKK4 > MAPK > BRaf > STAT-5 > STAT-1 > STAT-4 whereas pinostrobin depicts higher binding-energy with JAK-2 followed by B-Raf > MKK4 > VEGF > PI3K > MAPK > STAT-1 > STAT-4 > STAT-5. Further, molecular-dynamic simulation revealed that pinostrobin interacted with JAK-2 protein with binding-energy of 25.068 +/- 1.08 kJ/mol whereas acacetin interacted with both JAK-2 and Fyn with bindin-genergies of -23.466 +/- 0.9508 kJ/mol and -8.935 +/- 1.3108 kJ/mol respectively. High binding-energy, low inhibition-constant, and drug-likeness of acacetin and pinostrobin provide a clue for their usage as a JAK-2 inhibitor which could be useful for molecular/cell-target based in-vitro and in-vivo investigations.

Automated summary

This study investigates the inhibitory prospects of selected flavonoids on cancer-associated kinases through molecular docking analysis. Flavonoids acacetin and pinostrobin show high binding-energy with JAK-2, indicating their potential as JAK-2 inhibitors for cancer chemoprevention/treatment. High binding-energy, low inhibition-constant, and drug-likeness of acacetin and pinostrobin suggest their potential for further in-vitro and in-vivo investigations.