New aromatic/heteroaromatic propanesulfonylhydrazone compounds: Synthesis, physical properties and inhibition studies against carbonic anhydrase II (CAII) enzyme

Abstract

Some new aromatic/heteroaromatic propanesulfonylhydrazone derivatives (1-8) were synthesized and characterized by elemental analyses, FT-IR, H-1 NMR, C-13 NMR, LC/MS techniques. The geometry optimizations and spectral calculations were performed by using DFT/B3LYP/6-311G(d,p) basis set in Gaussian 09 program. The inhibition activities of the synthesized compounds on carbonic anhydrase II (CAII) isoenzyme have been investigated by comparing IC50 values. Acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide) AAZ, a clinically used in CAII inhibition has also been investigated as standard inhibitor. The best aromatic/heteroaromatic propanesulfonylhydrazone inhibitors of this isoform were o-aminobenzaldehydepropanesulfonylhydrazone (1) and thiophenecarboxyaldehyde propanesulfonylhydrazone (5) having the same IC50 (0.55 mM) value. The molecular descriptors for propanesulfonylhydrazones were obtained to develop structure activity relationship (SAR) model between experimental IC50 values and the molecular descriptors calculated by PM3-based SAR models in Hyperchem 8, respectively. The obtained models confirm the good carbonic anhydrase II (CAII) inhibition activity of the propanesulfonylhydrazone derivatives. The selected descriptors are sensitive both to the imine (CH=N) and NH2 groups that are responsible from higher activities of (1) and (5) in their series. (C) 2014 Elsevier B.V. All rights reserved.