New sulfonylhydrazones containing methane sulfonic acid hydrazıde havıng human anticarbonic anhydrase and antimicrobıal activıty: synthesis, spectroscopic characterization, electrochemical properties, and biological activıties

Abstract

In this work, new sulfonylhydrazones nomenclatured as 3,5-ditertbutylsalicylaldehyde methane­sulfonylhydrazone (II), 3-tertbutylsalicylaldehyde methanesulfonylhydrazone (III), and 5-bromosalicyl­aldehyde methanesulfonylhydrazone (IV) were synthesized by the reaction of methanesulfo­nicacidhydrazide (I) with 3,5-ditertbutylsalicylaldehyde, 3-tertbutylsalicyl aldehyde, and 5-bromosalicylaldehyde. The structures of the aromatic sulfonylhydrazones were determined by using elemental analysis, UV-Vis, FT-IR, 1H-NMR, and 13C-NMR methods. The structure of IV was also supported with the X-ray diffraction method. Sulfonamides were generally investigated for their inhibitory effects on human carbonic anhydrase isoenzymes (hCAs). Synthesized alkyl­sulfonylhydrazones have a sulfonamide group, which is the most important pharmacophore for the carbonic anhydrase (CA) inhibition efficiency like the reference agent acetazolamide (AAZ). The enzyme inhibition trends of alkylsulfonylhydrazones on the hCA I isoenzyme were qualitatively investigated by cyclic voltammetry (CV) and differantial pulse voltammetry (DPV). Also, the inhibition activities of sulfonylhydrazones were determined by using UV-Vis spectrophotometry, and their inhibition parameters, such as Km, IC50, and Ki, were calculated. Among the tested compounds, IV was found to be the most active compound on the hCA I isoenzyme with an IC50 value of 4.86×10–6 M, whereas II and III were found to be the least potent compounds on hCA I with an IC50 value of 3.96×10–4 M and 5.58×10–5 M, respectively. All of the compounds showed excellent inhibition activity against gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia) and gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidi), with minimum inhibitory concentration (MIC) values less than that of standard drugs (sulfamethoxazole and sulfisoxazole). In addition, all of the compounds exhibited excellent antifungal inhibition against C. albicans and A. fumigatus, with MIC values of 8–16 μg/ml, which were 2–4 fold higher than the standard drug fluconazole (32 μg/ml).

Keywords

• sulfonylhydrazones
• hCA I isoenzyme
• cyclic voltammetry (CV)
• minimum inhibitory concentrations (MICs)