Synthesis, characterizations of aryl-substituted dithiodibenzothioate derivatives, and investigating their anti-Alzheimer's properties

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dc.authoridCICEK, Baki/0000-0003-1257-1188
dc.authoridCALISIR, Umit/0000-0001-7699-2008
dc.authoridAdem, Sevki/0000-0003-2146-5870
dc.contributor.authorCalisir, Umit
dc.contributor.authorCamadan, Yasemin
dc.contributor.authorCicek, Baki
dc.contributor.authorAkkemik, Ebru
dc.contributor.authorEyupoglu, Volkan
dc.contributor.authorAdem, Sevki
dc.date.accessioned2024-12-24T19:28:11Z
dc.date.available2024-12-24T19:28:11Z
dc.date.issued2023
dc.departmentSiirt Üniversitesi
dc.description.abstractThe main objective of the present study was to synthesize potential inhibitor/activators of AChE and hCA I-II enzymes, which are thought to be directly related to Alzheimer's disease. Dithiodibenzothioate compounds were synthesized by thioesterification. Six different thiolate compounds produced were characterized by H-1-, C-13-NMR, FT-IR, LC-MS/MS methods. HOMO-LUMO calculations and electronic properties of all synthesized compounds were comprehensively illuminated with a semi-empirical molecular orbital (SEMO) package for organic and inorganic systems using Austin Model 1 (AM1)-Hamiltonian as implemented in the VAMP module of Materials Studio. In addition, the inhibition effects of these compounds for AChE and hCA I-II in vitro conditions were investigated. It was revealed that TE-1, TE-2, TE-3, TE-4, TE-5, and TE-6 compounds inhibited the AChE under in vitro conditions. TE-1 compound activated the enzyme hCA I while TE-2, TE-3 TE-4 compounds inhibited it. TE-5 and TE-6, on the other hand, did not exhibit a regular inhibition profile. Similarly, TE-1 activated the hCA II enzyme whereas TE-2, TE-3, TE-4, and TE-5 compounds inhibited it. TE-6 compound did not have a consistent inhibition profile for hCA II. Docking studies were performed with the compounds against AChE and hCA I-II receptors using induced-fit docking method. Molecular Dynamics (MD) simulations for best effective three protein-ligand couple were conducted to explore the binding affinity of the considered compounds in semi-real in-silico conditions. Along with the MD results, TE-1-based protein complexes were found more stable than TE-5. Based on these studies, TE-1 compound could be considered as a potential drug candidate for AD. Communicated by Ramaswamy H. Sarma
dc.description.sponsorshipSiirt University Scientific Research Projects Unit [2018-S_I_UM_UH-053]
dc.description.sponsorshipThis work has been supported by Siirt University Scientific Research Projects Unit with project number 2018-S_I_UM_UH-053.
dc.identifier.doi10.1080/07391102.2021.2024884
dc.identifier.endpage1845
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.issue5
dc.identifier.pmid35021953
dc.identifier.scopus2-s2.0-85122875382
dc.identifier.scopusqualityQ1
dc.identifier.startpage1828
dc.identifier.urihttps://doi.org/10.1080/07391102.2021.2024884
dc.identifier.urihttps://hdl.handle.net/20.500.12604/6942
dc.identifier.volume41
dc.identifier.wosWOS:000742277400001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Inc
dc.relation.ispartofJournal of Biomolecular Structure & Dynamics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241222
dc.subjectActivation
dc.subjectAlzheimer
dc.subjectdrug
dc.subjectinhibition
dc.subjectthioesterification
dc.titleSynthesis, characterizations of aryl-substituted dithiodibenzothioate derivatives, and investigating their anti-Alzheimer's properties
dc.typeArticle

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