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Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitorsTürkeş, CüneytAkocak, SuleymanIşık, MesutLolak, NebihTaslimi, ParhamDurgun, MustafaGülçin, İlhamiBudak, YakupBeydemir, ŞükrüAcetylcholinesterasebutyrylcholinesterasein silico studysulfamethazineα-glucosidasealpha-GlucosidasesCholinesterase InhibitorsGlycoside Hydrolase InhibitorsMolecular Docking SimulationStructure-Activity Relationshipacarbosealpha glucosidasealpha glucosidase inhibitorbenzenesulfonamide derivativecholinesterasecholinesterase inhibitorn (4,6 dimethylpyrimidin 2 yl) 4 (3 phenylureido)benzenesulfonamide derivativen (4,6 dimethylpyrimidin 2 yl) 4 [3 (3 chlorophenyl)ureido]benzenesulfonamiden (4,6 dimethylpyrimidin 2 yl) 4 [3 (3 tolyl)ureido]benzenesulfonamiden (4,6 dimethylpyrimidin 2 yl) 4 [3 (4 chlorophenyl)ureido]benzenesulfonamiden (4,6 dimethylpyrimidin 2 yl) 4 [3 (4 fluorophenyl)ureido]benzenesulfonamiden (4,6 dimethylpyrimidin 2 yl) 4 [3 (4 tolyl)ureido]benzenesulfonamiden (4,6 dimethylpyrimidin 2 yl) 4 [3 3,(4 dichlorophenyl)ureido]benzenesulfonamidetacrineunclassified drugglycosidase inhibitorsulfadimidineArticlebinding affinitycholinesterase inhibitionThe underlying cause of many metabolic diseases is abnormal changes in enzyme activity in metabolism. Inhibition of metabolic enzymes such as cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and α-glucosidase (α-GLY) is one of the accepted approaches in the treatment of Alzheimer’s disease (AD) and diabetes mellitus (DM). Here we reported an investigation of a new series of novel ureido-substituted derivatives with sulfamethazine backbone (2a-f) for the inhibition of AChE, BChE, and α-GLY. All the derivatives demonstrated activity in nanomolar levels as AChE, BChE, and α-GLY inhibitors with K I values in the range of 56.07–204.95 nM, 38.05–147.04 nM, and 12.80–79.22 nM, respectively. Among the many strong N-(4,6-dimethylpyrimidin-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide derivatives (2a-f) detected against ChEs, compound 2c, the 4-fluorophenylureido derivative, demonstrated the most potent inhibition profile towards AChE and BChE. A comprehensive ligand/receptor interaction prediction was performed in silico for the three metabolic enzymes providing molecular docking investigation using Glide XP, MM-GBSA, and ADME-Tox modules. The present research reinforces the rationale behind utilizing inhibitors with sulfamethazine backbone as innovative anticholinergic and antidiabetic agents with a new mechanism of action, submitting propositions for the rational design and synthesis of novel strong inhibitors targeting ChEs and α-GLY. Communicated by Ramaswamy H. Sarma. © 2021 Informa UK Limited, trading as Taylor & Francis Group.Taylor and Francis Ltd.2022Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/12593https://doi.org/10.1080/07391102.2021.19165990739-1102enJournal of Biomolecular Structure and Dynamicsinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/12593