Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors

Tuğrak M., Gül H. İ., Anıl B., Gülçin İ.

TURKISH JOURNAL OF CHEMISTRY, cilt.44, sa.6, ss.1601-1628, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 44 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.3906/kim-2007-37
  • Dergi Adı: TURKISH JOURNAL OF CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.1601-1628
  • Anahtar Kelimeler: Sulfonamide, benzamide, carbonic anhydrase, acetylcholinesterase, enzyme inhibition, SULFONAMIDE DERIVATIVES, ISOFORMS I, BUTYRYLCHOLINESTERASE
  • Atatürk Üniversitesi Adresli: Evet

Özet

N-(1-(4-Methoxyphenyl)-3-oxo-3((4-(N-(substituted)sulfamoyl)phenypamino)prop-1-en-1-yl)benzamides 3a - g were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and hCA II) inhibitory potencies. Structure elucidation of the compounds was carried out by H-1 NMR, C-13 NMR, and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I, hCA II, and AChE enzymes at nanomolar levels. Ki values were in the range of 4.07 +/- 0.38 - 29.70 +/- 3.18 nM for hCA I and 10.68 +/- 0.98 - 37.16 +/- 7.55 nM for hCA II while Ki values for AChE were in the range of 8.91 +/- 1.65 - 34.02 +/- 5.90 nM. The most potent inhibitors 3g (Ki = 4.07 +/- 0.38 nM, hCA I), 3c (Ki = 10.68 +/- 0.98 nM, hCA II), and 3f (Ki = 8.91 +/- 1.65 nM, AChE) can be considered as lead compounds of this study with their promising bioactivity results. Secondary sulfonamides showed promising enzyme inhibitory effects on AChE while primary sulfonamide derivative was generally effective on hCA I and hCA II isoenzymes.