PMID- 34569452
OWN - NLM
STAT- MEDLINE
DCOM- 20221227
LR  - 20230224
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 40
IP  - 23
DP  - 2022
TI  - Screening of Azadirachta indica phytoconstituents as GSK-3beta inhibitor and its 
      implication in neuroblastoma: molecular docking, molecular dynamics, MM-PBSA 
      binding energy, and in-vitro study.
PG  - 12827-12840
LID - 10.1080/07391102.2021.1977705 [doi]
AB  - 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-3beta is associated with the 
      pathogenesis of numerous human diseases, including cancer, metabolic disorder, 
      and Alzheimer's disease. In this study, Azadirachta indica 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-3beta. 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 from the Azadirachta indica, and its efficacy 
      on GSK-3beta 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-3beta (p-GSK-3beta 
      Ser9) in concentration-dependent manner. Our findings demonstrate that gedunin 
      may act as an effective GSK-3beta 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.
FAU - Chandel, Shivani
AU  - Chandel S
AD  - Department of Natural Products, National Institute of Pharmaceutical Education 
      and Research, Kolkata, India.
FAU - Singh, Rajveer
AU  - Singh R
AUID- ORCID: 0000-0002-6321-0617
AD  - Department of Natural Products, National Institute of Pharmaceutical Education 
      and Research, Kolkata, India.
FAU - Gautam, Anupam
AU  - Gautam A
AUID- ORCID: 0000-0002-6460-6525
AD  - Institute for Bioinformatics and Medical Informatics, University of Tubingen, 
      Tubingen, Germany.
AD  - International Max Planck Research School "From Molecules to Organisms", Max 
      Planck Institute for Developmental Biology, Tubingen, Germany.
FAU - Ravichandiran, Velayutham
AU  - Ravichandiran V
AD  - Department of Natural Products, National Institute of Pharmaceutical Education 
      and Research, Kolkata, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210927
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 2753-30-2 (gedunin)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Humans
MH  - Molecular Dynamics Simulation
MH  - Molecular Docking Simulation
MH  - Glycogen Synthase Kinase 3 beta
MH  - *Azadirachta
MH  - Glycogen Synthase Kinase 3
MH  - *Neuroblastoma/drug therapy
OTO - NOTNLM
OT  - Azadirachta indica compounds
OT  - GSK-3beta inhibitors
OT  - MM-PBSA
OT  - Molecular docking
OT  - molecular dynamic simulation
EDAT- 2021/09/28 06:00
MHDA- 2022/12/28 06:00
CRDT- 2021/09/27 08:53
PHST- 2021/09/28 06:00 [pubmed]
PHST- 2022/12/28 06:00 [medline]
PHST- 2021/09/27 08:53 [entrez]
AID - 10.1080/07391102.2021.1977705 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2022;40(23):12827-12840. doi: 10.1080/07391102.2021.1977705. 
      Epub 2021 Sep 27.