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Targeting p53-MDM2 Interaction by Natural Plant Products: A Novel Approach for Future Cancer Therapy
M.V. Raghavendra Rao1*, B.Vijay Raj2, Yogesh Acharya1, S. Jitendra Kumar Nayak3, SireeshaBala A1, Anusha C. Pawar3
1Avalon University School of Medicine, Curacao, Netherland Antilles
2Andhra Loyola College, Vijayawada, Andhra Pradesh, India
3Osmania University, Hyderabad, Telangana, India
*Address for Correspondence: Dr. M.V. Raghavendra Rao, Professor, Department of Microbiology, Dean of student affairs, Avalon University School of Medicine,
Sta. Rosaweg 122-124, Willemstad Curacao, Netherlands Antilles
ABSTRACT- P53 is a tumor suppressor gene with a well established role in causation of different human cancers. The p53-MDM2 interactions have become the cornerstone of intensive cancer based research due to their effective anti-cancer properties. These potential compounds are found in many traditional natural plant products. In the present context, there is a tremendous level of enthusiasm to evaluate the pharmacological potential of various natural plants used in traditional systems of medicine. The experimental efforts to carry out such biological screening of plants are still considerably high, and therefore, computer-aided drug design approaches have become attractive alternatives. Virtual screening has established itself as a dynamic and cost-effective technology to isolate compounds with pharmacological potential. The main aim of the present study is to identify a novel or similar or better drug like compound in comparison with that of the FDA approved drug Nutlin (potent MDM2-p53 inhibitor) from the Hamelia patens plant, through the Structure Based Virtual Screening, Docking and Molecular Dynamic Simulation studies, for future anti-cancer therapy for future implications as a therapeutic model.
Key-words- MDM2-p53 interaction, Natural Plant products, Virtual screening, Docking, Molecular dynamic simulation
MDM2 has been identified as a p53 interacting protein which represses p53 transcriptional activity. Design of non-peptide, small-molecule inhibitors, obtained from secondary plant products, that block the MDM2-p53 interaction has been sought as an attractive strategy to activate p53 for the treatment of cancer and other human diseases. Major advances have to be made in the design of these small-molecule inhibitors of the MDM2-p53 interaction as targeted therapies for advanced preclinical development or clinical trials, justifying the use of plant in traditional medicine practices. It is therefore recommended that more work be conducted to help optimally extract all the bioactive compounds in the plant and formulate into appropriate doses for the treatment.
How to cite this article:
Raghavendra Rao M.V., Raj BV, Acharya Y, Nayak SJK, SireeshaBala A, Pawar AC: Targeting p53-MDM2 Interaction by Natural Plant Products: A Novel Approach for Future Cancer Therapy. Int. J. Life. Sci. Scienti. Res., 2017; 3(2): 940-950. DOI:10.21276/ijlssr.2017.3.2.12