Acacetin and pinostrobin as a promising inhibitor of cancer-associated protein kinases
Autor: | Suaib Luqman, Ashish Meena, Shilpi Singh, Abha Meena |
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Rok vydání: | 2020 |
Předmět: |
MAPK/ERK pathway
Pharmacology Molecular Dynamics Simulation Toxicology medicine.disease_cause Disaccharides 03 medical and health sciences chemistry.chemical_compound 0404 agricultural biotechnology FYN Neoplasms medicine Humans Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology Adaptor Proteins Signal Transducing Flavonoids 0303 health sciences Acacetin Kinase Cancer Hydrogen Bonding 04 agricultural and veterinary sciences General Medicine medicine.disease Flavones 040401 food science Molecular Docking Simulation chemistry Cytochrome P-450 CYP2D6 Flavanones Thermodynamics Carcinogenesis Protein Kinases Food Science |
Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 151 |
ISSN: | 1873-6351 |
Popis: | 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 binding-energies 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. |
Databáze: | OpenAIRE |
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