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


AKOCAK S., Taslimi P., Lolak N., IŞIK M., DURGUN M., Budak Y., ...More

CHEMISTRY & BIODIVERSITY, vol.18, no.4, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 18 Issue: 4
  • Publication Date: 2021
  • Doi Number: 10.1002/cbdv.202000958
  • Journal Name: CHEMISTRY & BIODIVERSITY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: &#945, -glycosidase, acetylcholinesterase, butyrylcholinesterase, sulfaguanidine, in silico study
  • Anadolu University Affiliated: Yes

Abstract

A 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 alpha-glycosidase (alpha-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 K-I 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 alpha-GLY inhibitory effect, with K-I 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 alpha-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.