Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α-Glycosidase and Cholinesterase Inhibitors

Akocak S., Taslimi P., Lolak N., IŞIK M., Durgun M., Budak Y., ...Daha Fazla

Chemistry and Biodiversity, cilt.18, sa.4, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 18 Sayı: 4
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/cbdv.202000958
  • Dergi Adı: Chemistry and Biodiversity
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: acetylcholinesterase, butyrylcholinesterase, in silico study, sulfaguanidine, α-glycosidase
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

© 2021 Wiley-VHCA AG, Zurich, SwitzerlandA series of six N-carbamimidoyl-4-(3-substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives were investigated by spectrophotometric methods for α-glycosidase (α-GLY), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes associated with diabetes mellitus (DM) and Alzheimer's disease (AD). N-Carbamimidoyl-4-{[(3,4-dichlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2f) showed AChE and BChE inhibitory effects, with KI values of 515.98±45.03 nM and 598.47±59.18 nM, respectively, while N-carbamimidoyl-4-{[(3-chlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2e) showed strong α-GLY inhibitory effect, with KI values of 103.94±13.06 nM. The antidiabetic effects of the novel synthesized compounds are higher than their anti-Alzheimer's effects, because the inhibition effect of the compounds on the α-GLY with diabetic enzyme is greater than the effect on esterase enzymes. Indeed, inhibition of the metabolic enzymes is important for the treatment of DM and AD.