Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes
Visfatin (Nicotinamide phosphoribosyltransferase) is an adipokine implicated in mediating insulin resistance and exhibiting insulin mimetic effect and therefore represents a druggable target for diabetes therapy. About 3,844 peroxisome proliferator activated receptor gamma (PPARγ) agonists documente...
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doaj-53bba2ac2d834a1190ce5dfe0d6f42982020-11-25T01:20:03ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85352018-06-0172241249Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetesOlusola Olalekan Elekofehinti0Oluwamodupe Cecilia Ejelonu1Jean Paul Kamdem2Oluwaseun Benedicta Akinlosotu3Ayodeji Famuti4Damilare Desmond Adebowale5Opeyemi Iwaloye6Yetunde Irinyemi Bulu7Ige Joseph Kade8Joao Batista Teixeira Rocha9Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Ondo State, Nigeria; Corresponding author.Department of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State, NigeriaDepartamento de Ciências Biológicas da, Universidade Regional do Cariri – URCA, Crato, CE, BrazilDepartment of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State, NigeriaDepartment of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State, NigeriaDepartment of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State, NigeriaDepartment of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State, NigeriaDepartment of Plant Science and Biotechnology, Adekunle Ajasin University, Akungba Akoko, Ondo State, NigeriaDepartment of Biochemistry, Federal University of Technology Akure, Ondo State, NigeriaBioquimical Toxicologia; Departmento de Quimica, CCNE, Universidade Federal de Santa Maria, RS 97105-900, BrazilVisfatin (Nicotinamide phosphoribosyltransferase) is an adipokine implicated in mediating insulin resistance and exhibiting insulin mimetic effect and therefore represents a druggable target for diabetes therapy. About 3,844 peroxisome proliferator activated receptor gamma (PPARγ) agonists documented in Chembl database were docked with PPARγ and those with binding energy of >−9 kcal/mol having experimental EC50 of 0.1 to 1 nM were selected. The candidate compounds (27) were thereafter docked with visfatin (PDB ID: 4WQ6) using AutodockVina out of which eight compounds that ranked highest in binding energy (when compared with the co-crystallized ligand of visfatin: 3TQ) were selected. Compound 25 exhibited favorable ligand-protein molecular interaction and respected Lipinski’s rule of five and interestingly from the absorption, distribution, metabolism and excretion (ADME)-Toxicity analysis the compound have enhanced pharmacological properties than the current ligand of visfatin. Keywords: Nicotinamide phosphoribosyltransferase, Visfatin molecular docking, Type 2 diabetes, Adipokineshttp://www.sciencedirect.com/science/article/pii/S2314853517302068 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Olusola Olalekan Elekofehinti Oluwamodupe Cecilia Ejelonu Jean Paul Kamdem Oluwaseun Benedicta Akinlosotu Ayodeji Famuti Damilare Desmond Adebowale Opeyemi Iwaloye Yetunde Irinyemi Bulu Ige Joseph Kade Joao Batista Teixeira Rocha |
spellingShingle |
Olusola Olalekan Elekofehinti Oluwamodupe Cecilia Ejelonu Jean Paul Kamdem Oluwaseun Benedicta Akinlosotu Ayodeji Famuti Damilare Desmond Adebowale Opeyemi Iwaloye Yetunde Irinyemi Bulu Ige Joseph Kade Joao Batista Teixeira Rocha Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes Beni-Suef University Journal of Basic and Applied Sciences |
author_facet |
Olusola Olalekan Elekofehinti Oluwamodupe Cecilia Ejelonu Jean Paul Kamdem Oluwaseun Benedicta Akinlosotu Ayodeji Famuti Damilare Desmond Adebowale Opeyemi Iwaloye Yetunde Irinyemi Bulu Ige Joseph Kade Joao Batista Teixeira Rocha |
author_sort |
Olusola Olalekan Elekofehinti |
title |
Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes |
title_short |
Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes |
title_full |
Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes |
title_fullStr |
Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes |
title_full_unstemmed |
Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes |
title_sort |
discovery of potential visfatin activators using in silico docking and adme predictions as therapy for type 2 diabetes |
publisher |
SpringerOpen |
series |
Beni-Suef University Journal of Basic and Applied Sciences |
issn |
2314-8535 |
publishDate |
2018-06-01 |
description |
Visfatin (Nicotinamide phosphoribosyltransferase) is an adipokine implicated in mediating insulin resistance and exhibiting insulin mimetic effect and therefore represents a druggable target for diabetes therapy. About 3,844 peroxisome proliferator activated receptor gamma (PPARγ) agonists documented in Chembl database were docked with PPARγ and those with binding energy of >−9 kcal/mol having experimental EC50 of 0.1 to 1 nM were selected. The candidate compounds (27) were thereafter docked with visfatin (PDB ID: 4WQ6) using AutodockVina out of which eight compounds that ranked highest in binding energy (when compared with the co-crystallized ligand of visfatin: 3TQ) were selected. Compound 25 exhibited favorable ligand-protein molecular interaction and respected Lipinski’s rule of five and interestingly from the absorption, distribution, metabolism and excretion (ADME)-Toxicity analysis the compound have enhanced pharmacological properties than the current ligand of visfatin. Keywords: Nicotinamide phosphoribosyltransferase, Visfatin molecular docking, Type 2 diabetes, Adipokines |
url |
http://www.sciencedirect.com/science/article/pii/S2314853517302068 |
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