Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against Leukemia
The present study investigated the cytotoxic prospects of isolated compounds from Elaeodendron buchananii against leukemia, using computational tools. Comprehensive literature searches revealed only buchaninoside, mutangin, methyl 3β-acetoxy-11α, 19α, 28-trihydroxyurs-12-en-23-oic acid, 3β, 11α, 19α...
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Elsevier
2024-12-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750024001719 |
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| author | Ochuko L. Erukainure Jennifer Nambooze Chika I. Chukwuma Alhadji Malloum Aimen Aljoundi Ghazi Elamin |
| author_facet | Ochuko L. Erukainure Jennifer Nambooze Chika I. Chukwuma Alhadji Malloum Aimen Aljoundi Ghazi Elamin |
| author_sort | Ochuko L. Erukainure |
| collection | DOAJ |
| description | The present study investigated the cytotoxic prospects of isolated compounds from Elaeodendron buchananii against leukemia, using computational tools. Comprehensive literature searches revealed only buchaninoside, mutangin, methyl 3β-acetoxy-11α, 19α, 28-trihydroxyurs-12-en-23-oic acid, 3β, 11α, 19α-trihydroxyurs-12-en-23, 28-dioic acid, 3β-acetoxy-19α, 24, 28-trihydroxyurs-12-ene, 3-oxo-19α,28-dihydroxyurs-12-en-24-oic acid, and elabunin have been isolated from E. buchananii. The compounds were subjected to Density Functional Theory (DFT) and Molecular Dynamics (MD) analyses, with Fms-like tyrosine kinase (FLT3) and catalytic binding sites of Murine Leukemia Virus (MLV) as the target proteins in lukemia. Following DFT analysis, the structures of the compounds were optimized at the PW6B95D3/Def2-TZVP level of theory; their UV-Visible peaks were in the UV region, with mutangin, 3-oxo-19α,28-dihydroxyurs-12-en-24-oic acid and elabunin exhibiting one single peak. The potent Root-Mean-Square Deviation, Root-Mean-Square Fluctuation, solvent-accessible surface area and radius of gyration values indicated a strong and stable molecular interaction between the compounds and the proteins. These were further supported by high ∆G values, with MLV showing the best interaction. Per-residue decomposition plots also revealed high energy contributions in the interactions’ binding sites residues. These results indicate that the cytotoxic prospects of the isolated compounds against leukemia as indicated by its molecular interactions with FLT3 and MLV. |
| format | Article |
| id | doaj-art-46d6b9994bb64c33913d14af2a98e119 |
| institution | Kabale University |
| issn | 2214-7500 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj-art-46d6b9994bb64c33913d14af2a98e1192024-12-19T10:54:48ZengElsevierToxicology Reports2214-75002024-12-0113101788Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against LeukemiaOchuko L. Erukainure0Jennifer Nambooze1Chika I. Chukwuma2Alhadji Malloum3Aimen Aljoundi4Ghazi Elamin5Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa; Corresponding author.Department of Chemistry, School of Natural Sciences, Faculty of Agriculture and Natural Science, University of the Free State, Bloemfontein 9300, South AfricaCenter for Quality of Health and Living, Faculty of Health Sciences, Central University of Technology, Bloemfontein 9301, South AfricaDepartment of Chemistry, School of Natural Sciences, Faculty of Agriculture and Natural Science, University of the Free State, Bloemfontein 9300, South Africa; Department of Physics, Faculty of Science, The University of Maroua, Maroua, CameroonDepartment of Medicinal Chemistry, Collage of Pharmacy, Attahadi University, Tripoli V567-7M8, Libyan Arab Jamahiriya; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tripoli, Tripoli, Libyan Arab JamahiriyaDepartment of Anaesthesiology & Critical Care, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaThe present study investigated the cytotoxic prospects of isolated compounds from Elaeodendron buchananii against leukemia, using computational tools. Comprehensive literature searches revealed only buchaninoside, mutangin, methyl 3β-acetoxy-11α, 19α, 28-trihydroxyurs-12-en-23-oic acid, 3β, 11α, 19α-trihydroxyurs-12-en-23, 28-dioic acid, 3β-acetoxy-19α, 24, 28-trihydroxyurs-12-ene, 3-oxo-19α,28-dihydroxyurs-12-en-24-oic acid, and elabunin have been isolated from E. buchananii. The compounds were subjected to Density Functional Theory (DFT) and Molecular Dynamics (MD) analyses, with Fms-like tyrosine kinase (FLT3) and catalytic binding sites of Murine Leukemia Virus (MLV) as the target proteins in lukemia. Following DFT analysis, the structures of the compounds were optimized at the PW6B95D3/Def2-TZVP level of theory; their UV-Visible peaks were in the UV region, with mutangin, 3-oxo-19α,28-dihydroxyurs-12-en-24-oic acid and elabunin exhibiting one single peak. The potent Root-Mean-Square Deviation, Root-Mean-Square Fluctuation, solvent-accessible surface area and radius of gyration values indicated a strong and stable molecular interaction between the compounds and the proteins. These were further supported by high ∆G values, with MLV showing the best interaction. Per-residue decomposition plots also revealed high energy contributions in the interactions’ binding sites residues. These results indicate that the cytotoxic prospects of the isolated compounds against leukemia as indicated by its molecular interactions with FLT3 and MLV.http://www.sciencedirect.com/science/article/pii/S2214750024001719AnticancerComputationCytotoxicityElaeodendron buchananiiAnd Lukemia |
| spellingShingle | Ochuko L. Erukainure Jennifer Nambooze Chika I. Chukwuma Alhadji Malloum Aimen Aljoundi Ghazi Elamin Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against Leukemia Toxicology Reports Anticancer Computation Cytotoxicity Elaeodendron buchananii And Lukemia |
| title | Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against Leukemia |
| title_full | Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against Leukemia |
| title_fullStr | Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against Leukemia |
| title_full_unstemmed | Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against Leukemia |
| title_short | Computational and theoretical insights into the cytotoxic prospects of compounds isolated from Elaeodendron buchananii against Leukemia |
| title_sort | computational and theoretical insights into the cytotoxic prospects of compounds isolated from elaeodendron buchananii against leukemia |
| topic | Anticancer Computation Cytotoxicity Elaeodendron buchananii And Lukemia |
| url | http://www.sciencedirect.com/science/article/pii/S2214750024001719 |
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