Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties
BackgroundXanthones are dubbed as putative lead-like molecules for cancer drug design and discovery. This study was aimed at the synthesis, characterization, and in silico target fishing of novel xanthone derivatives.MethodsThe products of reactions of xanthydrol with urea, thiourea, and thiosemicar...
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Frontiers Media S.A.
2025-01-01
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| author | Wisam Taher Muslim Layth Jasim Mohammad Munaf M. Naji Isaac Karimi Matheel D. Al-Sabti Majid Jabir Mazin A. A. Najm Helgi B. Schiöth |
| author_facet | Wisam Taher Muslim Layth Jasim Mohammad Munaf M. Naji Isaac Karimi Matheel D. Al-Sabti Majid Jabir Mazin A. A. Najm Helgi B. Schiöth |
| author_sort | Wisam Taher Muslim |
| collection | DOAJ |
| description | BackgroundXanthones are dubbed as putative lead-like molecules for cancer drug design and discovery. This study was aimed at the synthesis, characterization, and in silico target fishing of novel xanthone derivatives.MethodsThe products of reactions of xanthydrol with urea, thiourea, and thiosemicarbazide reacted with α-haloketones to prepare the thiazolone compounds. Xanthydrol reacted sequentially with ethyl chloroacetate, hydrazine, carbon disulfide, and α-haloketones to prepare the dithiolane. The xanthydrol reacted with propargyl bromide and it submitted to click reaction with azide to prepare triazole ring.ResultsFinally, four novel xanthones derivatives including (E)-2-(2-(9H-xanthen-9-yl)hydrazono)-1,3-dithiolan-4-one (L3), 2-(2-(9H-xanthen-9-yl)hydrazinyl)thiazol-5(4H)-one (L5), 2-(9H-xanthen-9-ylamino)thiazol-5(4H)-one (L7), and 4-((9H-xanthen-9-yloxy)methyl)-1-(4-nitrophenyl)-1H-1,2,3-triazole (L9) were synthesized and characterized using thin layer chromatography, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance (1H and 13C). ADMET, Pfizer filter, adverse drug reaction, toxicity, antitarget interaction profiles, target fishing, kinase target screening, molecular docking validation, and protein and gene network analysis were computed for derivatives. Ligands obeyed Pfizer filter for drug-likeness, while all ligands were categorized as toxic chemicals. Major targets of all ligands were predicted to be kinases including Haspin, WEE2, and PIM3. Mitogen-activated protein kinase 1 was the hub gene of target kinase network of all derivatives. All the ligands were predicted to show hepatotoxic potentials, while L7 presented cardiac toxicity.ConclusionAcute leukemic T-cells were one of the top predicted tumor cell lines for these ligands. The possible antileukemic effects of synthesized xanthone derivatives are potentially very interesting and warrant further studies. |
| format | Article |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-aa7c1bb2d641467eb4e2d286d44f319a2025-08-20T02:12:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15116271511627Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical propertiesWisam Taher Muslim0Layth Jasim Mohammad1Munaf M. Naji2Isaac Karimi3Matheel D. Al-Sabti4Majid Jabir5Mazin A. A. Najm6Helgi B. Schiöth7Department of Pharmaceutical Chemistry, College of Pharmacy, Kufa University, Najaf City, IraqDepartment of Microbiology, College of Medicine, Babylon University, Hilla City, IraqClinical Laboratory Sciences, College of Pharmacy, Kufa University, Najaf City, IraqResearch Group of Bioengineering and Biotechnology, Laboratory for Computational Physiology, Department of Biology, Faculty of Science, Razi University, Kermanshah, IranDepartment of Science, College of Science, Uruk University, Baghdad, IraqDepartment of Applied Science, University of Technology, Baghdad, IraqDepartment of Pharmacy, Mazaya University Collage, Nasiriyah, IraqDepartment of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, SwedenBackgroundXanthones are dubbed as putative lead-like molecules for cancer drug design and discovery. This study was aimed at the synthesis, characterization, and in silico target fishing of novel xanthone derivatives.MethodsThe products of reactions of xanthydrol with urea, thiourea, and thiosemicarbazide reacted with α-haloketones to prepare the thiazolone compounds. Xanthydrol reacted sequentially with ethyl chloroacetate, hydrazine, carbon disulfide, and α-haloketones to prepare the dithiolane. The xanthydrol reacted with propargyl bromide and it submitted to click reaction with azide to prepare triazole ring.ResultsFinally, four novel xanthones derivatives including (E)-2-(2-(9H-xanthen-9-yl)hydrazono)-1,3-dithiolan-4-one (L3), 2-(2-(9H-xanthen-9-yl)hydrazinyl)thiazol-5(4H)-one (L5), 2-(9H-xanthen-9-ylamino)thiazol-5(4H)-one (L7), and 4-((9H-xanthen-9-yloxy)methyl)-1-(4-nitrophenyl)-1H-1,2,3-triazole (L9) were synthesized and characterized using thin layer chromatography, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance (1H and 13C). ADMET, Pfizer filter, adverse drug reaction, toxicity, antitarget interaction profiles, target fishing, kinase target screening, molecular docking validation, and protein and gene network analysis were computed for derivatives. Ligands obeyed Pfizer filter for drug-likeness, while all ligands were categorized as toxic chemicals. Major targets of all ligands were predicted to be kinases including Haspin, WEE2, and PIM3. Mitogen-activated protein kinase 1 was the hub gene of target kinase network of all derivatives. All the ligands were predicted to show hepatotoxic potentials, while L7 presented cardiac toxicity.ConclusionAcute leukemic T-cells were one of the top predicted tumor cell lines for these ligands. The possible antileukemic effects of synthesized xanthone derivatives are potentially very interesting and warrant further studies.https://www.frontiersin.org/articles/10.3389/fphar.2024.1511627/fullxanthonetotal synthesisADMETmolecular dockingnetwork analysistarget fishing |
| spellingShingle | Wisam Taher Muslim Layth Jasim Mohammad Munaf M. Naji Isaac Karimi Matheel D. Al-Sabti Majid Jabir Mazin A. A. Najm Helgi B. Schiöth Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties Frontiers in Pharmacology xanthone total synthesis ADMET molecular docking network analysis target fishing |
| title | Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties |
| title_full | Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties |
| title_fullStr | Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties |
| title_full_unstemmed | Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties |
| title_short | Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties |
| title_sort | synthesis characterization and computational evaluation of some synthesized xanthone derivatives focus on kinase target network and biomedical properties |
| topic | xanthone total synthesis ADMET molecular docking network analysis target fishing |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1511627/full |
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