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Analysis of Inhibition Potential of Nimbin and its Analogs against NF-κB Subunits p50 and p65: A Molecular Docking and Molecular Dynamics Study
Author(s):
Asiya Khan, Divyam Singh, Kamran Waidha, Sandeep Sisodiya, Pushparathinam Gopinath, Showket Hussian, Pranay Tanwar and Deepshikha Pande Katare* Pages 280 - 287 ( 8 )
Abstract:
<p>Background: Cancer remains the major cause of morbidity and mortality. The nuclear factor kappa-B (NF- κB) plays an indispensable role in cancer cell proliferation and drug resistance. The role of NF-κB is not only limited to tumor cell proliferation and suppression of apoptotic genes but it also induces EMT transition responsible for metastasis. Inhibition of the NF-κB pathway in cancer cells by herbal derivatives makes it a favorable yet promising target for cancer therapeutics. <p> Aim: The purpose of the study is to explore the inhibition potential of Nimbin and its analogs against NF-κB subunits p50 and p65. <p> Methods: In the present study, an herbal compound Nimbin and its derivative analogs were investigated to examine their impact on the p50 and p65 subunits of the NF-κB signaling pathway using <i>in silico</i> tools, namely molecular docking and simulation. <p> Results: The molecular docking analysis revealed that Nimbin and its analogs may bind to p50 and p65 subunits with dG bind values ranging from -33.23 to -50.49 Kcal/mol. Interestingly, molecular dynamic simulation for the NO5-p65 complex displayed a stable conformation and convergence when compared to the NO4-p50 complex. <p> Conclusion: These results indicate that NO5 may have a potential inhibitory effect against NF-κB subunit p65, which needs to be further validated in <i>in vitro</i> and in vivo systems. Also, the results obtained emphasize and pave the way for exploring the Nimbin scaffold against NF-κB inhibition for cancer therapeutics.</p>
Keywords:
Nimbin, p50, p65, molecular docking, simulation, natural compounds, signaling pathway.
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