Synthesis, characterization, crystal structure of novel bis-thiomethylcyclohexanone derivatives and their inhibitory properties against some metabolic enzymes


Bicer A., Taslimi P., Yakali G., GÜLÇİN İ., GÜLTEKİN M. S., TURGUT CİN G.

BIOORGANIC CHEMISTRY, cilt.82, ss.393-404, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 82
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.bioorg.2018.11.001
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.393-404
  • Anahtar Kelimeler: Bis-thiomethylcyclohexanone, Carbonic anhydrase, Acetylcholinesterase, Crystal structure, ANHYDRASE ISOENZYMES I, POTENT CARBONIC-ANHYDRASE, ACETYLCHOLINE ESTERASE, BIOLOGICAL EVALUATION, BOND FORMATION, MANNICH-BASES, 1ST SYNTHESIS, BUTYRYLCHOLINESTERASE, ANTIOXIDANT, BROMOPHENOLS
  • Akdeniz Üniversitesi Adresli: Evet

Özet

In this study, a series of novel bis-thiomethylcyclohexanone compounds (3a-3j) were synthesized by the addition of thio-Michael to the bis-chalcones under mild reaction conditions. The bis-thiomethylcyclohexanone derivatives (bis-sulfides) were characterized by H-1 NMR, C-13 NMR, FTIR and elemental analysis techniques. Furthermore, the molecular and crystal structures of 3h, 3i and 3j compounds were determined by single crystal X-ray diffraction studies. In this study, X-ray crystallography provided an alternative and often-complementary means for elucidating functional groups at the enzyme inhibitory site. Acetylcholinesterase (AChE) is a member of the hydrolase protein super family and has a significant role in acetylcholine-mediated neurotransmission. Here, we report the synthesis and determining of novel bis-thiomethylcyclohexanone compounds based hybrid scaffold of AChE inhibitors. The newly synthesized bis-thiomethylcyclohexanone compounds showed K-i values of in range of 39.14-183.23 nM against human carbonic anhydrase I isoenzyme (hCA I), 46.03-194.02 nM against human carbonic anhydrase II isoenzyme (hCA II), 4.55-32.64 nM against AChE and 12.77-37.38 nM against butyrylcholinesterase (BChE). As a result, novel bis-thiomethylcyclohexanone compounds can have promising anti Alzheimer drug potential and record novel hCA I, and hCA II enzymes inhibitor.