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, cilt.32, sa.1, ss.169-175, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 32 Sayı: 1
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1080/14756366.2016.1243536
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.169-175
  • Anahtar Kelimeler: Benzenesulfonamide, carbonic anhydrase, cytotoxicity, phenol, pyrazoline, CARBONIC-ANHYDRASE-IX, BIOLOGICAL EVALUATION, INHIBITORS SYNTHESIS, MANNICH-BASES, ISOENZYMES I, ISOFORMS I, HCA I, SULFONAMIDES, DERIVATIVES, SULFOCOUMARINS
  • Çukurova Üniversitesi Adresli: Hayır

Özet

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.