In silico investigation of tetrazole and oxadiazole compounds as inhibitors of the dengue virus NS5 protein: Synthesis, DFT, ADME and molecular docking analysis

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dc.authoridMUSATAT, AHMAD BADREDDIN/0000-0002-4137-4901
dc.authoridDemirci, Tuna/0000-0001-8933-4944
dc.contributor.authorDemirci, Tuna
dc.contributor.authorMusatat, Ahmad Badreddin
dc.contributor.authorKaya, Mustafa Oguzhan
dc.contributor.authorArslan, Mustafa
dc.date.accessioned2025-10-11T20:48:36Z
dc.date.available2025-10-11T20:48:36Z
dc.date.issued2025
dc.departmentDüzce Üniversitesien_US
dc.description.abstractThis study investigates the therapeutic potential of novel tetrazole and oxadiazole derivatives targeting the Dengue virus NS5 protein through an integrated computational and experimental approach. A series of nitrilesubstituted 1,4-dihydropyridine (1,4DHPs) derivatives were synthesized and converted into tetrazole and 1,3,4-oxadiazole analogs using established protocols. Structural characterization was performed via NMR, FT-IR, and elemental analysis. Molecular docking studies against the NS5 protein (PDB ID: 6KR2) revealed superior binding affinities for several compounds (Delta G = -7.18 to -9.58 kcal/mol), with compound 5 exhibiting the strongest interaction (Delta G = -9.58 kcal/mol, theoretical IC50 = 94.64 nM), outperforming the reference ligand SAH (Delta G = -7.18 kcal/mol). ADME profiling demonstrated favorable drug-likeness, acceptable solubility, bloodbrain barrier penetration, and CYP450 metabolic stability. DFT analyses elucidated electronic properties, including HOMO-LUMO gaps (2.72-4.80 eV) and electrophilicity indices (13.5-23.6 eV), correlating with observed bioactivity. Toxicity predictions identified compound-specific liabilities requiring optimization. These findings highlight the promise of tetrazole-oxadiazole hybrids as potent NS5 inhibitors, warranting further preclinical validation for Dengue therapeutic development.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [109T553]en_US
dc.description.sponsorshipThis work was produced from the MS Thesis Synthesis Of 1,3,4-Oxa-diazole and Tetrazole Substituted 1,4-Dihydropyridine and Pyridine Compound. This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) (1002 Number: 109T553) and we thank them for financial support.en_US
dc.identifier.doi10.1016/j.cbi.2025.111608
dc.identifier.issn0009-2797
dc.identifier.issn1872-7786
dc.identifier.pmid40543643en_US
dc.identifier.scopus2-s2.0-105009487143en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.cbi.2025.111608
dc.identifier.urihttps://hdl.handle.net/20.500.12684/22013
dc.identifier.volume418en_US
dc.identifier.wosWOS:001524411900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Ireland Ltden_US
dc.relation.ispartofChemico-Biological Interactionsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectDengue virus NS5en_US
dc.subjectMolecular dockingen_US
dc.subjectADMEen_US
dc.subjectDFTen_US
dc.subjectTetrazoleen_US
dc.subjectOxadiazoleen_US
dc.subject4-Dihydropyridineen_US
dc.titleIn silico investigation of tetrazole and oxadiazole compounds as inhibitors of the dengue virus NS5 protein: Synthesis, DFT, ADME and molecular docking analysisen_US
dc.typeArticleen_US

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