Amide derivatives with pyrazole carboxylic acids of 5-amino-1,3,4-thiadiazole 2-sulfonamide as new carbonic anhydrase inhibitors: Synthesis and investigation of inhibitory effects

Bulbul M., Kasimogullari R., KÜFREVİOĞLU Ö. İ.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.23, sa.6, ss.895-900, 2008 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 6
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1080/14756360701626173
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.895-900
  • Anahtar Kelimeler: Carbonic anhydrase, pyrazole carboxylic acids, inhibition, hydratase activity, esterase activity, CYCLIC OXALYL COMPOUNDS, ISOZYME-XII, ISOFORM-II, IN-VIVO, IX, SULFONAMIDES, DESIGN, AGENTS, IV
  • Atatürk Üniversitesi Adresli: Evet

Özet

Pyrazole carboxylic acid amides of 5-amino-1,3,4-thiadiazole-2-sulfonamide were synthesized from 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonyl chloride and 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride. Carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from human erythrocyte cells by the affinity chromatography method. The inhibitory effects of 5-amino-1,3,4-thiadiazole-2-sulfonamide 1, acetazolamide 2 and new synthesized amides on these isozymes have been studied in vitro. The I50 concentrations (the concentration of inhibitor producing a 50% inhibition of CA activity) against hydratase activity ranged from 1.2 to 2.2nM for hCA-I and from 0.4 to 2nM for hCA-II. The I50 values against esterase activity ranged from 1.4 to 8nM for hCA-I and from 1.3 to 6nM for hCA-II. The Ki values were observed between 8.210-5 to 6.210-4 M for hCA-I and between 2.910-4 to 8.210-4 M for hCA-II. The comparison of new synthesized amides to 5-amino-1,3,4-thiadiazole-2-sulfonamide 1, acetazolamide 2 indicated that the new synthesized compounds (18-23) inhibit CA activity more potently than the parent compounds.