Myricetin is a naturally omnipresent benzo-α-pyrone
flavonoids derivative; has potent anticancer activity.
Receptor tyrosine kinases family provides the decisive role in
cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat
cancer, owing to the evidences endorsed their over-expression on
cancer cells. This study is a concerted effort to explore the potent and specific multi-targeted inhibitor against RTKs and AR\ER employing molecular docking approach. IR, IGF1R, EGFR, VEGFR1, VEGFR2, and AR\ER were chosen as a
protein and natural compounds as a
ligand. Molecular docking procedure followed by using Maestro 9.6 (Schrödinger Inc). All natural compounds were docked with the X-ray crystal structures of selected
proteins by employing grid-based
ligand docking with energetics Maestro 9.6. IBS natural compounds docked with each selected
protein molecules by using GLIDE high throughput virtual screening. On the basis of Gscore, we selected 20 compounds from IBS (50,000 compounds) along with 68 anticancer compounds from published literature for GLIDE extra precision molecular docking. Calculated docking free energy yielded the excellent dock score for the
myricetin when docked with
proteins EGFR, IR, and AR\ER.
Protein-
ligand interactions profile highlighted that the lipophilic, hydrogen bonding and π-π stacking interactions play a central role in
protein-
ligand interactions at the active site. The results of MTT assay reveal that the
myricetin inhibit the viability and proliferation of
cancer cells in a dose-dependent manner. Treatment with the
myricetin led to down-regulation of
mRNA expression of EGFR, IR, mTOR, and Bcl-2. Although, further in vitro and in vivo experimental studies are required for the experimental validation of our findings.