Design and Synthesis of ?-O-Glucosylated 5-(Arylidene)-6-Aminouracils: Towards Water-Soluble 8-Aryl Xanthines as Effective Enzyme Inhibitors

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dc.authorid0000-0002-2882-6811
dc.authorid0000-0003-3276-1413
dc.contributor.authorPoslu, Ayse Halic
dc.contributor.authorErtik, Onur
dc.contributor.authorAbul, Nurgul
dc.contributor.authorTelli, Fatma Cetin
dc.contributor.authorGulcin, Ilhami
dc.contributor.authorKoz, Omer
dc.contributor.authorKoz, Gamze
dc.date.accessioned2026-02-08T15:14:49Z
dc.date.available2026-02-08T15:14:49Z
dc.date.issued2024
dc.departmentBursa Teknik Üniversitesi
dc.description.abstract8-Aryl xanthines are selective enzyme inhibitors modified from naturally occurring methylxanthines. However, the low water solubility of substituted xanthines restricts their clinical applications. We developed a strategy to improve the water solubility of biologically privileged 8-aryl xanthines. A series of glucosylated 5-(arylidene)-6-aminouracil was synthesized as 8-aryl-1,3-dimethyl xanthine precursors and fully characterized with spectroscopic methods. Koenigs-Knorr reaction was used to synthesize beta-O-glucosylated aromatic aldehydes which were then reacted with 5,6-diamino-1,3-dimethyluracil to obtain the corresponding 5-(arylidene)-6-aminouracils. The strategy was validated by the ring-closing reaction of a beta-O-glucosylated 5-(arylidene)-6-aminouracil derivative with iodine (I-2) in dimethoxyethane. The water solubility of the glucosylated 8-aryl-1,3-dimethyl xanthine and its non-glycosylated counterpart was compared. Glucosylation improved the water solubility of the compound. The effect of glucosylation on the bioactivity of the compounds was investigated by measuring their inhibition effect on some common enzymes. The glucosylated 8-aryl xanthine demonstrated significantly better efficiency. Molecular docking was performed to elucidate the ligand-protein interactions. Since the target enzymes are primarily related to brain disorders, the blood-brain barrier (BBB) penetration ability of 8-aryl xanthine partners was investigated. According to adsorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, glucosylated 8-aryl xanthine was found to be BBB permeable.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [119Z876]
dc.description.sponsorshipWe are grateful to the Scientific and Technological Research Council of Turkey (TUBITAK Project No. 119Z876) for financial support.
dc.identifier.doi10.1002/slct.202401406
dc.identifier.issn2365-6549
dc.identifier.issue26
dc.identifier.scopus2-s2.0-85197926078
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1002/slct.202401406
dc.identifier.urihttps://hdl.handle.net/20.500.12885/5455
dc.identifier.volume9
dc.identifier.wosWOS:001262680900001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistryselect
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzWOS_KA_20260207
dc.subjectNitrogen heterocycles
dc.subject8-aryl xanthine
dc.subjectGlucosylation
dc.subjectEnzymes
dc.subjectMolecular docking
dc.titleDesign and Synthesis of ?-O-Glucosylated 5-(Arylidene)-6-Aminouracils: Towards Water-Soluble 8-Aryl Xanthines as Effective Enzyme Inhibitors
dc.typeArticle

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