n/a
Abstract Title:

Screening ofphytoconstituents as GSK-3β inhibitor and its implication in neuroblastoma: molecular docking, molecular dynamics, MM-PBSA binding energy, and in-vitro study.

Abstract Source:

J Biomol Struct Dyn. 2021 Sep 27:1-14. Epub 2021 Sep 27. PMID: 34569452

Abstract Author(s):

Shivani Chandel, Rajveer Singh, Anupam Gautam, Velayutham Ravichandiran

Article Affiliation:

Shivani Chandel

Abstract:

Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, primary regulator of various cellular activities varying from glycogen metabolism to cell proliferation and regulation. GSK-3β is associated with the pathogenesis of numerous human diseases, including cancer, metabolic disorder, and Alzheimer's disease. In this study,compounds were selected and further screened on the BOILED-Egg model. The compounds showing good GIT absorption were docked with the crystal structure of GSK-3β. The compounds with high docking score were submitted for the molecular dynamic simulation (MDS) and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA). Based upon the MDS and MM-PBSA study, gedunin showed the highest binding energy throughout the MDS process. Gedunin was isolated fromthe, and its efficacy on GSK-3β inhibition was studied in the human neuroblastoma (SH-SY5Y) cells. Gedunin induced apoptosis and anti-proliferative activity by arresting G2/M phase, as evident by cell-cycle analysis. From immunoblot study, gedunin significantly enhanced the expression of an inhibitory form of GSK-3β (p-GSK-3βSer9) in concentration-dependent manner. Our findings demonstrate that gedunin may act as an effective GSK-3β inhibitor suggesting that this compound may be used for the management of neuroblastoma. Further preclinical and clinical investigation is desirable.Communicated by Ramaswamy H. Sarma.

Study Type : In Vitro Study

Print Options


Key Research Topics

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2024 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.