Harnessing high potential benzothiazole chalcones against dengue virus NS5 protein: A multi-faceted theoretical study through molecular docking, ADME, and DFT

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dc.authoridMUSATAT, AHMAD BADREDDIN/0000-0002-4137-4901;
dc.contributor.authorMusatat, Ahmad Badreddin
dc.contributor.authorDurmus, Tulay
dc.contributor.authorAtahan, Alparslan
dc.date.accessioned2025-10-11T20:48:37Z
dc.date.available2025-10-11T20:48:37Z
dc.date.issued2024
dc.departmentDüzce Üniversitesien_US
dc.description.abstractChalcones bearing tetralone, indanone and benzothiazole cores were synthesized successfully using a general Claisen-Schmidt condensation protocol. The prepared compounds were purified and structurally analyzed by 1H, 13C NMR, and FT-IR techniques. A multi-faceted theoretical approach, combining Density Functional Theory (DFT), molecular docking, and ADME predictions, was employed to evaluate their therapeutic potential. DFT calculations at the B3LYP/def2-TZVP level revealed key electronic properties, with TD3 compound demonstrating the highest chemical reactivity. Molecular Electrostatic Potential (MEP) and Reduced Density Gradient (RDG) analyses provided insights into the compounds' non-covalent interactions and charge distributions. Molecular docking studies against the NS5 protein (PDB: 6KR2) showed superior binding affinities for all three compounds compared to the control ligand SAH, with TD3 exhibiting the lowest binding energy (-8.41 kcal/ mol) and theoretical inhibition constant (689.31 nM). ADME predictions indicated favorable drug-like properties with concerns regarding aqueous solubility and potential P-glycoprotein interactions. Toxicity evaluations highlighted challenges, particularly in hepatotoxicity and carcinogenicity. The study identified TD3 as a promising lead compound for Dengue Virus NS5 inhibition, while also emphasizing the need for targeted modifications to address toxicity concerns. This research not only contributes to anti-dengue drug discovery efforts but also provides a robust methodological framework for the theoretical evaluation of similar small compounds in future investigations.en_US
dc.identifier.doi10.1016/j.abb.2024.110171
dc.identifier.issn0003-9861
dc.identifier.issn1096-0384
dc.identifier.pmid39366630en_US
dc.identifier.scopus2-s2.0-85205538737en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.abb.2024.110171
dc.identifier.urihttps://hdl.handle.net/20.500.12684/22021
dc.identifier.volume761en_US
dc.identifier.wosWOS:001347381900001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Incen_US
dc.relation.ispartofArchives of Biochemistryand Biophysicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectBenzothiazoleen_US
dc.subjectChalconeen_US
dc.subjectDFTen_US
dc.subjectMolecular dockingen_US
dc.subjectADMEen_US
dc.titleHarnessing high potential benzothiazole chalcones against dengue virus NS5 protein: A multi-faceted theoretical study through molecular docking, ADME, and DFTen_US
dc.typeArticleen_US

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