Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control
Isoxazole and oxadiazole derivatives inhibiting 3-hydroxykynurenine transaminase (3HKT) are potential larvicidal candidates. This study aims to identify more suited potential inhibitors of Anopheles gambiae 3HKT (Ag3HKT) through molecular docking and molecular dynamics simulation. A total of 958 com...
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Elsevier
2025-01-01
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| author | Eunice O. Adedeji Olubanke O. Ogunlana Gbolahan O. Oduselu Rainer Koenig Ezekiel Adebiyi Opeyemi S. Soremekun Segun Fatumo |
| author_facet | Eunice O. Adedeji Olubanke O. Ogunlana Gbolahan O. Oduselu Rainer Koenig Ezekiel Adebiyi Opeyemi S. Soremekun Segun Fatumo |
| author_sort | Eunice O. Adedeji |
| collection | DOAJ |
| description | Isoxazole and oxadiazole derivatives inhibiting 3-hydroxykynurenine transaminase (3HKT) are potential larvicidal candidates. This study aims to identify more suited potential inhibitors of Anopheles gambiae 3HKT (Ag3HKT) through molecular docking and molecular dynamics simulation. A total of 958 compounds were docked against Anopheles gambiae 3HKT (PDB ID: 2CH2) using Autodock vina and Autodock4. The top three identified hits were subjected to 300 ns molecular dynamics simulation using AMBER 18 and ADMET analysis using SWISSADME predictor and ADMETSAR. Replacement of alkyl attachment on C5 of isoxazole or oxadiazole derivative with a cycloalkyl group yielded compounds with lower binding energy than their straight chain counterparts. The top three compounds were brominated compounds, 2‐[3‐(4‐bromophenyl)‐1,2‐oxazol‐5‐yl]cyclopentane‐1‐carboxylic acid, 2-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, 3-[3-(4-bromo-2-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, and they had binding energies of −8.58, −8.25, and −8.18 kcal/mol in virtual screening against 2CH2 protein target, respectively. These compounds were predicted to be less toxic than temephos, a standard larvicide and more biodegradable than previously reported inhibitors. The three compounds exhibited a greater stabilizing effect on 2CH2 protein target than 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid, a previously reported inhibitor candidate with good larvicidal activity on Aedes aegypti. Further thermodynamic calculations revealed that the top three compounds possessed total binding energies (ΔGbind) of −26.64 kcal/mol, −24.26 kcal/mol and −14.11 kcal/mol, respectively, as compared to −12.02 kcal/mol for 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid. These compounds could be better larvicides than previously reported isoxazole or oxadiazole derivatives and safer than temephos. |
| format | Article |
| id | doaj-art-c32246511d324986a2761408e39465a1 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-c32246511d324986a2761408e39465a12025-01-17T04:51:48ZengElsevierHeliyon2405-84402025-01-01111e41633Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector controlEunice O. Adedeji0Olubanke O. Ogunlana1Gbolahan O. Oduselu2Rainer Koenig3Ezekiel Adebiyi4Opeyemi S. Soremekun5Segun Fatumo6Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria; Department of Biochemistry, Covenant University, Ota, Ogun State, Nigeria; Department of Biology, University of York, York, United KingdomCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria; Department of Biochemistry, Covenant University, Ota, Ogun State, Nigeria; Covenant Applied Informatics and Communication Africa Centre of Excellence, Covenant University, Ota, NigeriaCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, NigeriaInstitute for Infectious Diseases and Infection Control (IIMK, RG Systems Biology), Jena University Hospital, Am Klinikum 1, 07747, Jena, GermanyCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria; African Center of Excellence in Bioinformatics & Data Intensive Science, Makerere University, 10218, Kampala, Uganda; Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), G200, Im Neuenheimer Feld 280, 69120, Heidelberg, GermanyThe African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, UgandaThe African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda; Precision Healthcare University Research Institute, Queen Mary University of London, United Kingdom; Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, United Kingdom; Corresponding author. Precision Healthcare University Research Institute, Queen Mary University of London, Empire House, 67-75 New Road, London E1 1HH, United Kingdom.Isoxazole and oxadiazole derivatives inhibiting 3-hydroxykynurenine transaminase (3HKT) are potential larvicidal candidates. This study aims to identify more suited potential inhibitors of Anopheles gambiae 3HKT (Ag3HKT) through molecular docking and molecular dynamics simulation. A total of 958 compounds were docked against Anopheles gambiae 3HKT (PDB ID: 2CH2) using Autodock vina and Autodock4. The top three identified hits were subjected to 300 ns molecular dynamics simulation using AMBER 18 and ADMET analysis using SWISSADME predictor and ADMETSAR. Replacement of alkyl attachment on C5 of isoxazole or oxadiazole derivative with a cycloalkyl group yielded compounds with lower binding energy than their straight chain counterparts. The top three compounds were brominated compounds, 2‐[3‐(4‐bromophenyl)‐1,2‐oxazol‐5‐yl]cyclopentane‐1‐carboxylic acid, 2-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, 3-[3-(4-bromo-2-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, and they had binding energies of −8.58, −8.25, and −8.18 kcal/mol in virtual screening against 2CH2 protein target, respectively. These compounds were predicted to be less toxic than temephos, a standard larvicide and more biodegradable than previously reported inhibitors. The three compounds exhibited a greater stabilizing effect on 2CH2 protein target than 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid, a previously reported inhibitor candidate with good larvicidal activity on Aedes aegypti. Further thermodynamic calculations revealed that the top three compounds possessed total binding energies (ΔGbind) of −26.64 kcal/mol, −24.26 kcal/mol and −14.11 kcal/mol, respectively, as compared to −12.02 kcal/mol for 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid. These compounds could be better larvicides than previously reported isoxazole or oxadiazole derivatives and safer than temephos.http://www.sciencedirect.com/science/article/pii/S240584402500012X1,2,4-Oxadiazole3HKTIsoxazolesLarvicideMosquitoVector control |
| spellingShingle | Eunice O. Adedeji Olubanke O. Ogunlana Gbolahan O. Oduselu Rainer Koenig Ezekiel Adebiyi Opeyemi S. Soremekun Segun Fatumo Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control Heliyon 1,2,4-Oxadiazole 3HKT Isoxazoles Larvicide Mosquito Vector control |
| title | Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control |
| title_full | Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control |
| title_fullStr | Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control |
| title_full_unstemmed | Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control |
| title_short | Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control |
| title_sort | molecular docking and molecular dynamics simulation studies of inhibitor candidates against anopheles gambiae 3 hydroxykynurenine transaminase and implications on vector control |
| topic | 1,2,4-Oxadiazole 3HKT Isoxazoles Larvicide Mosquito Vector control |
| url | http://www.sciencedirect.com/science/article/pii/S240584402500012X |
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