Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis

Background: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, the enhancers of incretin are used for the treatment of diabetes. The non-glycaemic actions of these drugs (under developmental stage) also proved that repurposing of these molecules may be advantageous for other few complicated disorders like...

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Autores principales:	Nehru Sai Suresh Chalichem, Srikanth Jupudi, Venkata Ramesh Yasam, Duraiswamy Basavan
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Alzheimer's disease Calebin A Dipeptidyl peptidase-IV Induced fit docking CD26 activity assay and in silico analysis Miscellaneous systems and treatments RZ409.7-999
Acceso en línea:	https://doaj.org/article/fd9ef96a030a49378f8d1dcf67396cdb
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spelling	oai:doaj.org-article:fd9ef96a030a49378f8d1dcf67396cdb2021-12-02T04:59:22ZDipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis0975-947610.1016/j.jaim.2021.08.008https://doaj.org/article/fd9ef96a030a49378f8d1dcf67396cdb2021-10-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0975947621001832https://doaj.org/toc/0975-9476Background: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, the enhancers of incretin are used for the treatment of diabetes. The non-glycaemic actions of these drugs (under developmental stage) also proved that repurposing of these molecules may be advantageous for other few complicated disorders like cardiovascular diseases, Parkinson's disease, Alzheimer's disease, etc. Objective: The present study was aimed to investigate the DPP-IV inhibitory potential of Calebin-A, one of the constituents of Curcuma longa. Material and methods: The phytoconstituent was subjected for various in silico studies (using Schrödinger Suite) like, Docking analysis, molecular mechanics combined with generalized Born model and solvent accessibility method (MMGBSA) and Induced fit docking (IFD) after validating the protein using Ramachandran plot. Further, the protein-ligand complex was subjected to molecular dynamic simulation studies for 50 nanoseconds. And finally, the results were confirmed through enzyme inhibition study. Results: In silico results revealed possible inhibitory binding interactions in the catalytic pocket (importantly Glu205, Glu206 and Tyr 662 etc.) and binding affinity in terms of glide g-score and MMGBSA dG bind values were found to be −6.2 kcal/mol and −98.721 kcal/mol. Further, the inhibitory action towards the enzyme was confirmed by an enzyme inhibition assay, in which it showed dose-dependent inhibition, with maximum % inhibition of 55.9 at 26.3 μM. From molecular dynamic studies (50 nanoseconds), it was understood that Calebin A was found to be stable for about 30 nanoseconds in maintaining inhibitory interactions. Conclusion: From the in silico and in vitro analysis, the current research emphasizes the consideration of Calebin A to be as a promising or lead compound for the treatment of several ailments where DPP-IV action is culprit.Nehru Sai Suresh ChalichemSrikanth JupudiVenkata Ramesh YasamDuraiswamy BasavanElsevierarticleAlzheimer's diseaseCalebin ADipeptidyl peptidase-IVInduced fit dockingCD26 activity assay and in silico analysisMiscellaneous systems and treatmentsRZ409.7-999ENJournal of Ayurveda and Integrative Medicine, Vol 12, Iss 4, Pp 663-672 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer's disease Calebin A Dipeptidyl peptidase-IV Induced fit docking CD26 activity assay and in silico analysis Miscellaneous systems and treatments RZ409.7-999
spellingShingle	Alzheimer's disease Calebin A Dipeptidyl peptidase-IV Induced fit docking CD26 activity assay and in silico analysis Miscellaneous systems and treatments RZ409.7-999 Nehru Sai Suresh Chalichem Srikanth Jupudi Venkata Ramesh Yasam Duraiswamy Basavan Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis
description	Background: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, the enhancers of incretin are used for the treatment of diabetes. The non-glycaemic actions of these drugs (under developmental stage) also proved that repurposing of these molecules may be advantageous for other few complicated disorders like cardiovascular diseases, Parkinson's disease, Alzheimer's disease, etc. Objective: The present study was aimed to investigate the DPP-IV inhibitory potential of Calebin-A, one of the constituents of Curcuma longa. Material and methods: The phytoconstituent was subjected for various in silico studies (using Schrödinger Suite) like, Docking analysis, molecular mechanics combined with generalized Born model and solvent accessibility method (MMGBSA) and Induced fit docking (IFD) after validating the protein using Ramachandran plot. Further, the protein-ligand complex was subjected to molecular dynamic simulation studies for 50 nanoseconds. And finally, the results were confirmed through enzyme inhibition study. Results: In silico results revealed possible inhibitory binding interactions in the catalytic pocket (importantly Glu205, Glu206 and Tyr 662 etc.) and binding affinity in terms of glide g-score and MMGBSA dG bind values were found to be −6.2 kcal/mol and −98.721 kcal/mol. Further, the inhibitory action towards the enzyme was confirmed by an enzyme inhibition assay, in which it showed dose-dependent inhibition, with maximum % inhibition of 55.9 at 26.3 μM. From molecular dynamic studies (50 nanoseconds), it was understood that Calebin A was found to be stable for about 30 nanoseconds in maintaining inhibitory interactions. Conclusion: From the in silico and in vitro analysis, the current research emphasizes the consideration of Calebin A to be as a promising or lead compound for the treatment of several ailments where DPP-IV action is culprit.
format	article
author	Nehru Sai Suresh Chalichem Srikanth Jupudi Venkata Ramesh Yasam Duraiswamy Basavan
author_facet	Nehru Sai Suresh Chalichem Srikanth Jupudi Venkata Ramesh Yasam Duraiswamy Basavan
author_sort	Nehru Sai Suresh Chalichem
title	Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis
title_short	Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis
title_full	Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis
title_fullStr	Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis
title_full_unstemmed	Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis
title_sort	dipeptidyl peptidase-iv inhibitory action of calebin a: an in silico and in vitro analysis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/fd9ef96a030a49378f8d1dcf67396cdb
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Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis

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