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Targeting Small Molecule Tyrosine Kinases by Polyphenols: New Move Towards Anti-tumor Drug Discovery

Author(s):

Nikhil S. Sakle, Shweta A. More, Sachin A. Dhawale and Santosh N. Mokale*   Pages 1 - 31 ( 31 )

Abstract:


Background: Cancer is a complex disease involving genetic and epigenetic alteration that allows cells to escape normal homeostasis. Kinases play a crucial role in signaling pathways that regulates cell functions. Deregulation of kinases leads to a variety of pathological changes, activating cancer cell proliferation and metastases. The molecular mechanism of cancer is complex and dysregulation of tyrosine kinases like anaplastic lymphoma kinase (ALK), Bcr-Abl (Fusion gene found in patient with chronic myelogenous leukemia (CML), JAK (Janus Activated Kinase), Src family kinases (SFKs), ALK (Anaplastic lymphoma Kinase), c-MET (Mesenchymal- Epithelial Transition), EGFR (Epidermal Growth Factor receptor), PDGFR (Platelet Derived Growth Factor Receptor), RET (Rearranged during Transfection), VEGFR (Vascular Endothelial Growth Factor Receptor) play major role in the process of carcinogenesis. Recently kinase inhibitors have overcome many problems of traditional cancer chemotherapy as they effectively separate out normal, non-cancer cells as well as rapidly multiplying cancer cells.

Methods: Electronic databases were searched to explore the small molecule tyrosine kinases by polyphenols with the help of docking study (Glide-7.6 program interfaced with Maestro-v11.3 of Schrödinger 2017) to show the binding energies of polyphenols inhibitor with different tyrosin kinases in order to differentiate between the targets.

Results: From the literature survey, it was observed that the number of polyphenols derived from natural sources alters the expression and signaling cascade of tyrosine kinase in various tumor models. Therefore, the development of polyphenols as a tyrosin kinase inhibitor against targeted proteins is regarded as an upcoming trend for chemoprevention.

Conclusion: In this review, we have discussed about the role of polyphenols as chemoreceptive which will help in future for the development and discovery of novel semisynthetic anticancer agents coupled with polyphenols.

Keywords:

Tyrosin kinase, Polyphenols, Docking analysis

Affiliation:

Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad-431001, Maharashtra, Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad-431001, Maharashtra, Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad-431001, Maharashtra, Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad-431001, Maharashtra



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