Molecular docking and investigation of 4-(benzylideneamino)- and 4-(benzylamino)-benzenesulfonamide derivatives as potent AChE inhibitors
- 35 Downloads
The discovery of acetylcholinesterase inhibitors is important for the treatment of Alzheimer’s disease (AD), known as the most common type of dementia. Due to the side effects of commonly used acetylcholinesterase inhibitors, studies for the detection of new inhibitors are increasing day by day. In this study, we investigated the effects of some sulfonamide derivatives (S1–S4 and S1i–S4i) on AChE enzymes. The best pose of the active compounds to understand the mechanism of possible inhibition in interaction of enzyme-sulfonamide derivative were performed docking studies after in vitro experimental results. ADME-related physicochemical and pharmacokinetic properties of the synthesized 4-aminobenzenesulfonamide derivatives were the compatibility with Lipinski’s rule of five. We found that the synthesized derivatives of sulfonamides show potential inhibitor properties for AChE with Ki constants in the range of 2.54 ± 0.22–299.60 ± 8.73 µM. The derivatives of sulfonamides exhibited different inhibition type. We determined that the derivatives (S1, S1i, S3, and S3i) showed a competitive inhibition effect, whereas others (S2, S2i, S4, and S4i) showed mixed-type inhibition. As a result, the sulfonamide derivatives can be used as an alternative acetylcholinesterase inhibitor due to this effect. Inhibitors with fewer side effects, are thought to be important in the treatment of AD.
KeywordsSulfonamide derivatives Alzheimer AChE inhibitor Molecular docking Pharmacokinetic properties
The authors are grateful for the financial support provided by the Research Foundation of Harran University (Project no. 16180).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Caglayan C, Demir Y, Kucukler S, Taslimi P, Kandemir FM, Gulçin İ (2019) The effects of hesperidin on sodium arsenite-induced different organ toxicity in rats on metabolic enzymes as antidiabetic and anticholinergics potentials: a biochemical approach. J Food Biochem 43:e12720. https://doi.org/10.1111/jfbc.12720 CrossRefPubMedGoogle Scholar
- Ignasik M, Bajda M, Guzior N, Prinz M, Holzgrabe U, Malawska B (2012) Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1, 3-dione derivatives as dual-binding site acetylcholinesterase inhibitors. Arch Pharm 345:509–516. https://doi.org/10.1002/ardp.201100423 CrossRefGoogle Scholar
- Kołaczek A, Fusiarz I, Ławecka J, Branowska D (2014) Biological activity and synthesis of sulfonamide derivatives: a brief review. Chemik 68:620–628Google Scholar
- Türkeş C, Söyüt H, Beydemir Ş (2015) Human serum paraoxonase-1 (hPON1): in vitro inhibition effects of moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium. J Enzyme Inhib Med Chem 30:622–628. https://doi.org/10.3109/14756366.2014.959511 CrossRefPubMedGoogle Scholar
- Türkeş C, Arslan M, Demir Y, Çoçaj L, Nixha AR, Beydemir Ş (2019a) Synthesis, biological evaluation and in silico studies of novel N-substituted phthalazine sulfonamide compounds as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg Chem 89:103004. https://doi.org/10.1016/j.bioorg.2019.103004 CrossRefPubMedGoogle Scholar
- Wager TT, Chandrasekaran RY, Hou X, Troutman MD, Verhoest PR, Villalobos A, Will Y (2010) Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes. ACS Chem Neurosci 1:420–434. https://doi.org/10.1021/cn100007x CrossRefPubMedPubMedCentralGoogle Scholar
- Yamali C, Gul HI, Ece A, Taslimi P, Gulcin I (2018) Synthesis, molecular modeling, and biological evaluation of 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes. Chem Biol Drug Des 91:854–866. https://doi.org/10.1111/cbdd.13149 CrossRefPubMedGoogle Scholar