Synthesis, Structure and Evaluation of the <i>N</i>-(2-Acetyl-4-(styryl)phenyl)-4-benzenesulfonamide Derivatives for Anticholinesterase and Antioxidant Activities

• Main Authors: Malose J. Mphahlele, Samantha Gildenhuys, Sizwe J. Zamisa
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Crystals
• Subjects: <i>N</i>-(2-Acetyl-4-bromophenyl)-4-methylbenzenesulfonamide; Suzuki-Miyaura cross-coupling; X-ray; hydrogen bonding; cholinesterases; antioxidant effect
• Online Access: https://www.mdpi.com/2073-4352/11/4/341

<i>N</i>-(2-Acetyl-4-bromophenyl)-4-methylbenzenesulfonamide (<b>2</b>) was transformed into 5-(4-methoxymethylstyryl)-2-(<i>p</i>-tolylsulfonamido)acetophenone (<b>3a</b>) and 5-(4- trifluoromethylstyryl)-2-(<i>p</i>-tolylsulfonamido)acetophenone (<b>3b</b>). 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 (<b>1</b>), 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 <b>3a</b> 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.