Synthesis and characterization of novel substituted thiophene derivatives and discovery of their carbonic anhydrase and acetylcholinesterase inhibition effects


Cetin A. , Turkan F., Taslimi P., GÜLÇİN İ.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, vol.33, no.3, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 33 Issue: 3
  • Publication Date: 2019
  • Doi Number: 10.1002/jbt.22261
  • Title of Journal : JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Keywords: acetylcholinesterase, carbonic anhydrase, enzyme inhibition, synthesis, thiophene, GLUTATHIONE-S-TRANSFERASE, BIOLOGICAL EVALUATION, ISOENZYMES I, CRYSTAL-STRUCTURE, MANNICH-BASES, 1ST SYNTHESIS, BUTYRYLCHOLINESTERASE, CHALCONES, ANTICANCER, BROMOPHENOLS

Abstract

Novel substituted thiophene derivatives (1, 2a-e, 3, and 4) were synthesized and their structures were characterized by infrared radiation, nuclear magnetic resonance, and mass analysis. These novel substituted thiophene derivatives were effective inhibitor compounds of the carbonic anhydrase I and II isozymes (hCA I and II), and acetylcholinesterase (AChE) enzyme with K-i values in the range of 447.28 to 1004.65 nM for hCA I, 309.44 to 935.93 nM for hCA II, and 0.28 to 4.01 nM for AChE, respectively. Novel substituted thiophene derivatives can be good candidate drugs for the treatment of some diseases like neurological disorders, epilepsy, glaucoma, gastric and duodenal ulcers, mountain sickness, or osteoporosis as carbonic anhydrase isozymes inhibitors, and for the treatment of Alzheimer's and Parkinson's diseases as acetylcholinesterase inhibitors.