In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus
Aldose reductase and glycogen synthase kinase 3β (GSK3β) represent two of the ideal drug targets in diabetes due to their role in the pathogenesis of diabetes. Studies have shown that plant compounds provide therapeutics in diabetes management. This study identified some compounds in S. mombin as du...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | Informatics in Medicine Unlocked |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352914822002635 |
| _version_ | 1797951513071452160 |
|---|---|
| author | B.O. Ajiboye T.M. Fagbola I.M. Folorunso A.W. Salami O.N. Aletile B.A. Akomolede F.I. Ayemoni K.I. Akinfemiwa V.O. Anwo M.I. Ojeleke B.E. Oyinloye |
| author_facet | B.O. Ajiboye T.M. Fagbola I.M. Folorunso A.W. Salami O.N. Aletile B.A. Akomolede F.I. Ayemoni K.I. Akinfemiwa V.O. Anwo M.I. Ojeleke B.E. Oyinloye |
| author_sort | B.O. Ajiboye |
| collection | DOAJ |
| description | Aldose reductase and glycogen synthase kinase 3β (GSK3β) represent two of the ideal drug targets in diabetes due to their role in the pathogenesis of diabetes. Studies have shown that plant compounds provide therapeutics in diabetes management. This study identified some compounds in S. mombin as dual inhibitors of aldose reductase and GSK3β. S. mombin compounds (n = 100) were docked with both aldose reductase and GSK3β; and the nine top scoring compounds were identified. The plant compounds were further investigated with MM-GBSA, ADME, HOMO/LUMO and constructed QSAR model to determine its stability with the targets, evaluate its drug-likeness, identify reactive molecules and predict its bioactivities against the proteins. The results show that the nine-top scoring compounds (Quercetin, Catechin, Ellagic acid, Tangeretin, Estradiol, Epicatechin, linalool, 2-Nitroethyl benzene, and Eugenol) attained stability with the proteins, and they also demonstrated excellent drug-like and pharmacokinetic characteristics, which qualifies them as drug candidates. The results identified linalool as the most reactive compound and Catechin as the most chemically inert molecules among the leads. The constructed QSAR model validated the molecular docking results by predicting satisfactory biological activities of the plant compounds against both targets. Although, the current findings have identified S. mombin compounds as dual inhibitors of aldose reductase and GSK3β, experimental studies are ongoing to validate the findings made by this study. |
| first_indexed | 2024-04-10T22:32:46Z |
| format | Article |
| id | doaj.art-54f9da45938a45a091b8b71ccae53633 |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-04-10T22:32:46Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-54f9da45938a45a091b8b71ccae536332023-01-17T04:07:17ZengElsevierInformatics in Medicine Unlocked2352-91482023-01-0136101126In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitusB.O. Ajiboye0T.M. Fagbola1I.M. Folorunso2A.W. Salami3O.N. Aletile4B.A. Akomolede5F.I. Ayemoni6K.I. Akinfemiwa7V.O. Anwo8M.I. Ojeleke9B.E. Oyinloye10Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Nigeria; Institute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, PMB 5454, Ado, Ekiti, 360001, Nigeria; Corresponding author. Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, PMB 373, Oye, Ekiti, 371104, Nigeria.Department of Computer Science, Faculty of Science, Federal University Oye-Ekiti, PMB 373, Oye, Ekiti, NigeriaDepartment of Biochemistry, Federal University of Technology Akure, NigeriaPhytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, NigeriaPhytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, NigeriaPhytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, NigeriaPhytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, NigeriaPhytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, NigeriaPhytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, NigeriaPhytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, NigeriaInstitute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, PMB 5454, Ado, Ekiti, 360001, Nigeria; Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti, 360001, Nigeria; Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South AfricaAldose reductase and glycogen synthase kinase 3β (GSK3β) represent two of the ideal drug targets in diabetes due to their role in the pathogenesis of diabetes. Studies have shown that plant compounds provide therapeutics in diabetes management. This study identified some compounds in S. mombin as dual inhibitors of aldose reductase and GSK3β. S. mombin compounds (n = 100) were docked with both aldose reductase and GSK3β; and the nine top scoring compounds were identified. The plant compounds were further investigated with MM-GBSA, ADME, HOMO/LUMO and constructed QSAR model to determine its stability with the targets, evaluate its drug-likeness, identify reactive molecules and predict its bioactivities against the proteins. The results show that the nine-top scoring compounds (Quercetin, Catechin, Ellagic acid, Tangeretin, Estradiol, Epicatechin, linalool, 2-Nitroethyl benzene, and Eugenol) attained stability with the proteins, and they also demonstrated excellent drug-like and pharmacokinetic characteristics, which qualifies them as drug candidates. The results identified linalool as the most reactive compound and Catechin as the most chemically inert molecules among the leads. The constructed QSAR model validated the molecular docking results by predicting satisfactory biological activities of the plant compounds against both targets. Although, the current findings have identified S. mombin compounds as dual inhibitors of aldose reductase and GSK3β, experimental studies are ongoing to validate the findings made by this study.http://www.sciencedirect.com/science/article/pii/S2352914822002635DiabetesAldose reductaseGlycogen synthase 3βMolecular dockingDrug candidateDrug discovery |
| spellingShingle | B.O. Ajiboye T.M. Fagbola I.M. Folorunso A.W. Salami O.N. Aletile B.A. Akomolede F.I. Ayemoni K.I. Akinfemiwa V.O. Anwo M.I. Ojeleke B.E. Oyinloye In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus Informatics in Medicine Unlocked Diabetes Aldose reductase Glycogen synthase 3β Molecular docking Drug candidate Drug discovery |
| title | In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus |
| title_full | In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus |
| title_fullStr | In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus |
| title_full_unstemmed | In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus |
| title_short | In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus |
| title_sort | in silico identification of chemical compounds in spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus |
| topic | Diabetes Aldose reductase Glycogen synthase 3β Molecular docking Drug candidate Drug discovery |
| url | http://www.sciencedirect.com/science/article/pii/S2352914822002635 |
| work_keys_str_mv | AT boajiboye insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT tmfagbola insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT imfolorunso insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT awsalami insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT onaletile insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT baakomolede insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT fiayemoni insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT kiakinfemiwa insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT voanwo insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT miojeleke insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus AT beoyinloye insilicoidentificationofchemicalcompoundsinspondiasmombintargetingaldosereductaseandglycogensynthasekinase3btoabatediabetesmellitus |