Carbonic anhydrase inhibitors: Synthesis, characterization and inhibition activities of furan sulfonylhydrazones against carbonic anhydrase I (hCA I)

Abstract

The methane sulfonic acide hydrazide (1) was used to obtain furan sulfonylhydrazones; 2acetylfuranmethanesulfonylhydrazone (2), 2-furaldehydemethanesulfonylhydrazone (3), 5-nitro-2furaldehydemethanesulfonylhydrazone (4). The structures of furan sulfonylhydrazones were determined by using elemental analysis, FT-IR, H-1 NMR, C-13 NMR and UV vis methods. The structure of 5nitro-2-furaldehydemethanesulfonylhydrazone (4) was also supported with X-ray difraction method and found that compound 4 was crystallized in triclinic, space group PT. In order to gain insight into the structure of the compounds, we performed computational studies by using 6-311G(d,p) basic set in which B3LYP correlation function was implemented. The geometry of the sulfonylhydrazones were optimized at DFT method with Gaussian 09 program package and the global reactivity descriptors were also calculated by this basic set. The enzyme inhibition activities of the sulfonylhydrazones were investigated on carbonic anhydrase I (hCA I) isoenzyme and their activity parameters (Km, IC50 and Ki) were calculated by spectrophotometric method. And also, their inhibitor effects were also investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods. Inhibition results show that compound 4 containing electron withdrawing group (NO2) has higher inhibition effect on hCA I isoenzyme than other's. (C) 2015 Elsevier B.V. All rights reserved.