Analysis of Inhibition Potential of Nimbin and its Analogs against NF-κB Subunits p50 and p65: A Molecular Docking and Molecular Dynamics Study


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Аннотация

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.

Aim:The purpose of the study is to explore the inhibition potential of Nimbin and its analogs against NF-κB subunits p50 and p65.

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 in silico tools, namely molecular docking and simulation.

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 -50.49Kcal/mol. Interestingly, molecular dynamic simulation for the NO5-p65 complex displayed a stable conformation and convergence when compared to the NO4-p50 complex.

Conclusion:These results indicate that NO5 may have a potential inhibitory effect against NF-κB subunit p65, which needs to be further validated in in vitro 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.

Авторлар туралы

Asiya Khan

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University

Email: info@benthamscience.net

Divyam Singh

Division of Molecular Oncology & Molecular Diagnostics, ICMR-National Institute of Cancer Prevention and Research, Ministry of Health & Family

Email: info@benthamscience.net

Kamran Waidha

Division of Molecular Oncology & Molecular Diagnostics, ICMR-National Institute of Cancer Prevention and Research, Ministry of Health & Family

Email: info@benthamscience.net

Sandeep Sisodiya

Division of Molecular Oncology & Molecular Diagnostics, ICMR-National Institute of Cancer Prevention and Research, Ministry of Health & Family

Email: info@benthamscience.net

Pushparathinam Gopinath

Department of Chemistry, College of Engineering and Technology,, SRM Institute of Science and Technology,

Email: info@benthamscience.net

Showket Hussian

Division of Molecular Oncology & Molecular Diagnostics, ICMR-National Institute of Cancer Prevention and Research, Ministry of Health & Family

Email: info@benthamscience.net

Pranay Tanwar

Laboratory Oncology Unit, Rotary Cancer Center, All India Institute of Medical Sciences

Email: info@benthamscience.net

Deepshikha Katare

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

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