Synthesis of N-phenylsulfonamide derivatives and investigation of some esterase enzymes inhibiting properties

• Published in: Bioorganic chemistry 2020-11, Vol.104, p.104279, Article 104279
• Main Authors: Akin Kazancioglu, Elif, Senturk, Murat
• Format: Article
• Language: English
• Subjects: 4-Phenyl-sulfonamide; Acetylcholinesterase - metabolism; Aniline; Butyrylcholinesterase - metabolism; Carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrases - metabolism; Cholinesterase; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Dose-Response Relationship, Drug; Enzyme inhibition; Humans; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Molecular Structure; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104279

[Display omitted] In this study, synthesis of nine N-phenylsulfonamide derivatives was designed by starting from aniline, which is the simplest aromatic amine. These compounds were obtained in yields between 69 and 95%. Inhibitory properties of synthesized compounds on carbonic anhydrase I (CA I), CA II isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were investigated. Inhibitors of CA isoenzymes are important therapeutic targets, particularly due to their preventive/activation potential in the treatment of diseases such as edema, glaucoma, cancer and osteoporosis. Cholinesterase inhibitors are valuable compounds that can be used in many different therapeutic applications, including Alzheimer's disease. The compound 8 for CA I, AChE and BChE, 2 for CA II showed a very active inhibition profile (KI 45.7 ± 0.46 for CA I, 33.5 ± 0.38 nM for CA II, 31.5 ± 0.33 nM for AChE and 24.4 ± 0.29 nM for BChE). The results indicate that these N-phenyl-sulfonamide derivatives are potent CA and cholinesterases and new potential drugs.