Synthesis of novel bis-sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase

Bicer A., Kaya R., ANIL B., TURGUT CİN G., GÜLÇİN İ., GÜLTEKİN M. S.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.33, sa.11, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33 Sayı: 11
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1002/jbt.22401
  • Dergi Adı: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: acetylcholinesterase, bis-sulfide, butyrylcholinesterase, bis-sulfone, carbonic anhydrase, TROUT ONCORHYNCHUS-MYKISS, ERYTHROCYTE ISOZYMES I, CRYSTAL-STRUCTURE, ANTICHOLINERGIC ACTIVITIES, BIOLOGICAL EVALUATION, HYDROGEN-PEROXIDE, 1ST SYNTHESIS, POTENT, ANTIOXIDANT, SULFOXIDES
  • Akdeniz Üniversitesi Adresli: Evet

Özet

In this study, a series of novel bis-sulfone compounds (2a-2j) were synthesized by oxidation of the bis-sulfides under mild reaction conditions. The bis-sulfone derivatives were characterized by H-1-NMR, C-13-NMR, Fourier-transform infrared spectroscopy, and elemental analysis techniques. Nuclear Overhauser effect experiments were performed to determine the orientation of the sulfonyl groups in bis-sulfone derivatives. Here, we report the synthesis and testing of novel bis-sulfone compound-based hybrid scaffold of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the development of novel molecules toward the therapy of Alzheimer's disease. The novel synthesized bis-sulfone compounds demonstrated K-i values between 11.4 +/- 3.4 and 70.7 +/- 23.2 nM on human carbonic anhydrase I isozyme (hCA I), 28.7 +/- 6.6 to 77.6 +/- 5.6 nM on human carbonic anhydrase II isozyme (hCA II), 18.7 +/- 2.61 to 95.4 +/- 25.52 nM on AChE, and 9.5 +/- 2.1 to 95.5 +/- 1.2 nM on BChE enzymes. The results showed that novel bis-sulfone derivatives can have promising drug potential for glaucoma, leukemia, epilepsy, and Alzheimer's disease, which are associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes.