Synthesis, Structure and Evaluation of the N-(2-Acetyl-4-(styryl)phenyl)-4-benzenesulfonamide Derivatives for Anticholinesterase and Antioxidant Activities
Source abstract
Abstract
N-(2-Acetyl-4-bromophenyl)-4-methylbenzenesulfonamide (2) was transformed into 5-(4-methoxymethylstyryl)-2-(p-tolylsulfonamido)acetophenone (3a) and 5-(4- trifluoromethylstyryl)-2-(p-tolylsulfonamido)acetophenone (3b). Their structures were determined using a combination of NMR (1H & 13C) and mass spectroscopic as well as single crystal X-ray diffraction techniques. These compounds and the corresponding precursor, 2-amino-5-bromoacetophenone (1), were evaluated through enzymatic assays in vitro for inhibitory effect against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities as well as antioxidant effect through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. Molecular docking was performed on 3a to determine plausible protein–ligand interactions on a molecular level. Their drug likeness properties (absorption, distribution, metabolism, and excretion) and ability to cross the blood–brain barrier (BBB) have also been predicted at theoretical level.
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Research context
OpenAlex topics: Cholinesterase and Neurodegenerative Diseases · Computational Drug Discovery Methods · Enzyme function and inhibition
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa
Department of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa
School of Chemistry and Physics, College of Agriculture, Engineering and Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
Funding
National Research Foundation (ZA)
References (50)
Show source-provided references
1. Effect of resveratrol and pterostilbene on aging and longevity10.1002/biof.1400 ↗
2. Resveratrol and pterostilbene: A comparative overview of their chemistry, biosynthesis, plant sources and pharmacological properties10.7324/JAPS.2019.90717 ↗
3. Artasensi, A., Alessandro, P., Vistoli, G., and Fumagalli, L. (2020). Type 2 diabetes mellitus: A review of multi-target drugs. Molecules, 25.10.3390/molecules25081987 ↗
4. Identification and evaluation of a napyradiomycin as a potent Nrf2 activator: Anti-oxidative and anti-inflammatory activities10.1016/j.bioorg.2020.104434 ↗
5. Wu, P.-S., Li, Y.-S., Kuo, Y.-C., Tsai, S.-J.J., and Lin, C.-C. (2019). Preparation and evaluation of novel transfersomes combined with the natural antioxidant resveratrol. Molecules, 24.10.3390/molecules24030600 ↗
6. Designing of promising medicinal scaffolds for Alzheimer’s disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches10.1016/j.bioorg.2019.103138 ↗
7. Development of diarylpentadienone analogues as alpha-glucosidase inhibitor: Synthesis, in vitro biological and in vivo toxicity evaluations, and molecular docking analysis10.1016/j.bioorg.2020.104277 ↗
8. Evaluation of anti-pigmentary effect of synthetic sulfonylamino chalcone10.1016/j.ejmech.2010.01.049 ↗
9. Sulfonamide chalcones: Synthesis and in vitro exploration for therapeutic potential against Brugia malayi10.1016/j.ejmech.2016.08.042 ↗
10. On the in silico and in vitro anticancer activity of sulfonamide chalcones: Potential JNKK3 inhibitors
11. Synthesis, anti-inflammatory and antioxidant activity of ring-A-monosubstituted chalcone derivatives10.1007/s00044-014-1007-z ↗
12. Different reactivity to glutathione but similar tumor cell toxicity of chalcones and their quinolinone analogues10.1007/s00044-019-02384-8 ↗
13. Sulphonamide chalcones: Conformationally diverse yet optically similar10.1016/j.molstruc.2019.126896 ↗
14. Benzenesulfonyl incorporated chalcones: Synthesis, structural and optical properties10.1016/j.molstruc.2020.127845 ↗
15. Conformational variability in sulfonamide chalcone hybrids: Crystal structure and cytotoxicity
16. Tandem chalcone-sulfonamide hybridization, cyclization and further Claisen–Schmidt condensation: Tuning molecular diversity through reaction time and order and catalyst10.1016/j.arabjc.2017.11.005 ↗
17. Structural insights into a novel anticancer sulfonamide chalcone10.1039/C7NJ03523C ↗
18. Solvent-driven structural adaptation in a novel anticancer sulfonamide chalcone10.1016/j.molstruc.2018.07.059 ↗
19. Hydrogen bonding in sulfonamides10.1002/jps.1157 ↗
20. Crystal structure of N-(adamantan-1-yl)-5-(dimethylamino)naphthalene-1-sulfonamide, C22H28N2O2S
21. Characteristic hydrogen bonding observed in the crystals of aromatic sulfonamides: 1D chain assembly of molecules and chiral discrimination on crystallization10.1021/acs.cgd.9b00159 ↗
22. Sulfonamide molecular crystals: Structure, sublimation thermodynamic characteristics, molecular packing, hydrogen bonds networks10.1021/cg400666v ↗
23. Structural, spectroscopic and nonlinear optical properties of sulfonamide derivatives; experimental and theoretical study10.1016/j.molstruc.2019.127393 ↗
24. Intramolecular hydrogen bonding in derivatives of beta-alanine and gamma-amino butyric acid; model studies for the folding of unnatural polypeptide backbones10.1021/ja00082a029 ↗
25. The blood-brain barrier in Alzheimer’s disease10.1016/j.nbd.2016.07.007 ↗
26. Blood-brain barrier: From physiology to disease and back10.1152/physrev.00050.2017 ↗
27. Drug delivery to the brain in Alzheimer’s disease: Consideration of the blood-brain barrier10.1016/j.addr.2011.12.005 ↗
28. High throughput artificial membrane permeability assay for blood-brain barrier10.1016/S0223-5234(03)00012-6 ↗
29. In vitro cytotoxicity of novel 2,5,7-tricarbo-substituted indoles derived from 2-amino-5-bromo-3-iodoacetophenone10.1016/j.bmc.2016.07.056 ↗
30. (2016). Bruker, APEX-3, SAINT+, Version 6.02 (Includes XPREP and SADABS), Bruker AXS Inc.
31. OLEX2: A complete structure solution, refinement and analysis program10.1107/S0021889808042726 ↗
32. SHELXT-Integrated space-group and crystal-structure determination
33. Crystal structure refinement with SHELXL
34. Mercury CSD 2.0–New features for the visualization and investigation of crystal structures10.1107/S0021889807067908 ↗
35. Turner, M.J., McKinnon, J.J., Wolff, S.K., Grimwood, D.J., Spackman, P.R., Jayatilaka, D., and Spackman, M.A. (2017). CrystalExplorer17, University of Western Australia.
36. Fingerprinting intermolecular interactions in molecular crystals10.1039/B203191B ↗
37. synthesis of furocoumarin–stilbene hybrids as potential multifunctional drugs against multiple biochemical targets associated with Alzheimer’s disease10.1016/j.bioorg.2020.103997 ↗
38. A rapid and simple method for the measurement of nitrite and nitrate in plasma by high performance capillary electrophoresis10.1006/bbrc.1994.1542 ↗
39. Antitumor effect of para-toluenesulfonamide against lung cancer xenograft in a mouse model
40. A new reagent for dehydrating primary amides under mild conditions10.1021/ja01611a102 ↗
41. N-Donor 2-(sulfonamido)benzamide ligands, their palladium(II) coordination species and C–C coupling catalysis efficiencies10.1016/j.molstruc.2019.07.054 ↗
42. Grabowski, S.J. (2021). Intramolecular hydrogen bond energy and its decomposition–O–H···O interactions. Crystals, 11.10.3390/cryst11010005 ↗
43. Mphahlele, M.J., Onwu, E.E., and Maluleka, M.M. (2021). Spectroscopic, X-ray diffraction and density functional theory study of intra- and intermolecular hydrogen bonds in ortho-(4-tolylsulfonamido)benzamides. Molecules, 26.10.3390/molecules26040926 ↗
44. Intramolecular hydrogen bonding in medicinal chemistry10.1021/jm100087s ↗
45. Substituent effects in halogen bonding complexes between aromatic donors and acceptors: A comprehensive ab initio study10.1039/c1cp22456e ↗
46. Halogen bonding versus hydrogen bonding: A molecular orbital perspective10.1002/open.201100015 ↗
47. Understanding non-covalent interactions in larger molecular complexes from first principles
48. Sulfonamide derivatives of 2-amino-1-phenylethane as suitable cholinesterase inhibitors10.4314/tjpr.v13i5.13 ↗
49. Rate-limited steps of human oral absorption and QSAR studies10.1023/A:1020444330011 ↗
50. A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules10.1002/cmdc.201600182 ↗