Çalışır, ÜmitCamadan, YaseminÇiçek, BakiAkkemik, EbruEyüpoğlu, VolkanAdem, Şevki2022-01-202022-01-202021Çalışır, Ü., Camadan, Y., Çiçek, B., Akkemik, E., Eyüpoğlu, V., & Adem, Ş. (2021). Synthesis, characterizations of aryl-substituted dithiodibenzothioate derivatives, and investigating their anti-Alzheimer's properties. Journal of Biomolecular Structure and Dynamics,https://hdl.handle.net/11494/3707This work has been supported by Siirt University Scientific Research Projects Unit with project number 2018-S_I_UM_UH-053.The 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 1H-, 13C-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. Sarmaeninfo:eu-repo/semantics/closedAccessActivationAlzheimerDrugInhibitionThioesterificationArticleArticle in press10.1080/07391102.2021.2024884Q1Q1