In silico Molecular Docking Study to Search New SGLT2 Inhibitor based on Dioxabicyclo[3.2.1] Octane Scaffold.

AutoDock Vina SGLT2 inhibitors Vibrio parahaemolyticus diabetes dioxabicyclo[3.2.1] octane molecular docking.

Journal

Current computer-aided drug design
ISSN: 1875-6697
Titre abrégé: Curr Comput Aided Drug Des
Pays: United Arab Emirates
ID NLM: 101265750

Informations de publication

Date de publication:
2020
Historique:
received: 25 05 2018
revised: 01 06 2018
accepted: 18 10 2018
pubmed: 23 10 2018
medline: 18 12 2020
entrez: 23 10 2018
Statut: ppublish

Résumé

Diabetes is a leading cause of high mortality rate in the world. Recently, SGLT2 inhibitors showed the promising result to treat diabetes and therefore several molecules are approved by the US FDA. SGLT2 inhibitors were designed based on dioxabicyclo[3.2.1] octane with the aim to search new lead molecule. The molecular structures were drawn in ChemBiodraw ultra and molecular docking study was performed by AutoDock Vina 1.5.6 software. The LogP and toxicity were predicted online using AlogP and Lazar in-silico respectively. Among all the designed molecules, SK306 showed the maximum binding affinity against the 3dh4 SGLT2 protein of Vibrio parahaemolyticus. LogP values were also calculated in order to determine the lipophilic property of the best binding molecules which show LogP 2.82-3.79 in the range for good absorption and elimination, also predicted to be non-toxic. SGLT2 inhibitors were designed based on the dioxabicyclo [3.2.1] octane resulting in a new lead molecule with high binding affinity; also these molecules were predicted to be noncarcinogenic with low LogP.

Sections du résumé

BACKGROUND BACKGROUND
Diabetes is a leading cause of high mortality rate in the world. Recently, SGLT2 inhibitors showed the promising result to treat diabetes and therefore several molecules are approved by the US FDA.
OBJECTIVE OBJECTIVE
SGLT2 inhibitors were designed based on dioxabicyclo[3.2.1] octane with the aim to search new lead molecule.
METHODS METHODS
The molecular structures were drawn in ChemBiodraw ultra and molecular docking study was performed by AutoDock Vina 1.5.6 software. The LogP and toxicity were predicted online using AlogP and Lazar in-silico respectively.
RESULTS RESULTS
Among all the designed molecules, SK306 showed the maximum binding affinity against the 3dh4 SGLT2 protein of Vibrio parahaemolyticus. LogP values were also calculated in order to determine the lipophilic property of the best binding molecules which show LogP 2.82-3.79 in the range for good absorption and elimination, also predicted to be non-toxic.
CONCLUSION CONCLUSIONS
SGLT2 inhibitors were designed based on the dioxabicyclo [3.2.1] octane resulting in a new lead molecule with high binding affinity; also these molecules were predicted to be noncarcinogenic with low LogP.

Identifiants

pubmed: 30345926
pii: CAD-EPUB-93850
doi: 10.2174/1573409914666181019165821
doi:

Substances chimiques

Bridged Bicyclo Compounds, Heterocyclic 0
Sodium-Glucose Transporter 2 Inhibitors 0
dioxabicyclo(3.2.1)octane 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

145-154

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Shubham Kumar (S)

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara - 144 411, Punjab, India.

Gopal L Khatik (GL)

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara - 144 411, Punjab, India.

Amit Mittal (A)

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara - 144 411, Punjab, India.

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Classifications MeSH