title: Screening and biological evaluation of myricetin as a multiple target inhibitor insulin, epidermal growth factor, and androgen receptor; in silico and in vitro.
abstract: 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.
authors.affiliation: Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India, 151001.
authors.forename: Pushpendra
authors.initials: P
authors.lastname: Singh
authors.forename: Felix
authors.initials: F
authors.lastname: Bast
mesh_terms: D059002:Androgen Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D062126:Databases, Chemical; D004353:Drug Evaluation, Preclinical; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D007329:Insulin Antagonists / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D062105:Molecular Docking Simulation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D012984:Software; D013816:Thermodynamics
chemical_list: D059002:Androgen Receptor Antagonists; D005419:Flavonoids; D007328:Insulin; D007329:Insulin Antagonists; D008024:Ligands; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D004815:Epidermal Growth Factor; C040015:myricetin