Designing, synthesis and bioactivities of 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl] benzenesulfonamides


GÜL H. İ. , METE E., Eren S. E. , Sakagami H., Yamali C. , Supuran C. T.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.32, no.1, pp.169-175, 2017 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 32 Issue: 1
  • Publication Date: 2017
  • Doi Number: 10.1080/14756366.2016.1243536
  • Title of Journal : JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Page Numbers: pp.169-175
  • Keywords: Benzenesulfonamide, carbonic anhydrase, cytotoxicity, phenol, pyrazoline, CARBONIC-ANHYDRASE-IX, BIOLOGICAL EVALUATION, INHIBITORS SYNTHESIS, MANNICH-BASES, ISOENZYMES I, ISOFORMS I, HCA I, SULFONAMIDES, DERIVATIVES, SULFOCOUMARINS

Abstract

In this study, 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl] benzenesulfonamide (1-9) types compounds were synthesized and their chemical structures were confirmed by H-1 NMR, C-13 NMR and HRMS spectra. Cytotoxic and carbonic anhydrase (CA) inhibitory effects of the compounds were investigated. Cytotoxicity experiments pointed out that compound 4, (4-[5-(4-chlorophenyl)-3-(4-hydroxyphenyl)-4,5dihydro- pyrazol-1-yl] benzenesulfonamide), exerting the highest tumor selectivity (TS) and potency selectivity expression (PSE) values, can be considered as a lead compound of this study in terms of development of novel anticancer agents. All synthesized sulfonamides showed a good inhibition profile on hCA IX and XII in the range of 53.5-923nM and 6.2-95 nM, respectively. These compounds were 2.5-13.4 times more selective for the inhibition of hCA XII versus hCA IX, except compound 2 which had similar inhibitory action towards both isoenzymes.