Copper(II) sulfonamide complexes having enzyme inhibition activities on carbonic anhydrase I: synthesis, characterization and inhibition studies

• Published in: Journal of the Iranian Chemical Society 2022, Vol.19 (1), p.55-69
• Main Authors: Uzun, Demet, Balaban Gündüzalp, Ayla, Parlakgümüş, Gökhan, Özmen, Ümmühan Özdemir, Özbek, Neslihan, Aktan, Ebru
• Format: Article
• Language: English
• Subjects: Acetazolamide; Analytical Chemistry; Biochemistry; Carbonic anhydrase; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chloride; Coordination compounds; Copper; Copper chloride; Enzymes; Inorganic Chemistry; Mathematical analysis; Nitrophenol; Organic Chemistry; Original Paper; Physical Chemistry; Substrates; Sulfonamides; Sulfonic acid
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-021-02287-9

In our present study, copper(II) sulfonamide complexes titled as bis-(2 acetylfuranmethanesulfonylhydrazone) copper(II) chloride, bis-(2-furaldehydemethanesulfonylhydrazone)copper(II) chloride and bis-(5-nitro-2 furaldehydemethanesulfonylhydrazone)copper(II) chloride were synthesized using aromatic sulfonylhydrazones derived from methane sulfonic acid hydrazide. The structures of copper(II) sulfonamides were determined by using LC–MS, FT-IR and UV–Vis methods, magnetism and conductivity measurements, and also electrochemical studies. In order to gain insight into the structure of the copper(II) complexes, computational studies were performed by using DFT/B3LYP/6-311G( d , p ) basis set with the Gaussian 09 program package. In general, sulfonamides and their derivatives are researched for their inhibitory effects on carbonic anhydrase isoenzymes (CAs). Synthesized copper(II) complexes have also sulfonamide group which is the most important pharmacophore for CA inhibition efficiency like acetazolamide (AAZ) as positive control. The carbonic anhydrase I (CA I) inhibition of copper(II) complexes which goes on competitively was determined by using UV–Vis spectrophotometer technique, and their inhibition parameters such as K m , IC 50 and K i were calculated. Among tested compounds, bis-(5-nitro-2 furaldehydemethanesulfonylhydrazone) copper(II) chloride was found to be the most active complex on CA I isoenzyme with IC 50 value of 7.03 × 10 −5  M. The enzyme inhibition trends of copper(II) sulfonamides on CA I isoenzyme were also investigated by CV and differential pulse voltammetry (DPV) techniques, qualitatively. The substrate of p -nitrophenyl acetate (PNPA) was hydrolyzed by CA I and produced p -nitrophenol (PNP). The electrochemical studies showed that when the concentration of the inhibitor was increased, the reduction peak current of PNP produced by the hydrolysis of PNPA was decreased by enzyme inhibition. Graphic Abstract