Synthesis, characterization, and inhibition study of novel substituted phenylureido sulfaguanidine derivatives as α-glycosidase and cholinesterase inhibitors.

Akocak, Suleyman; Taslimi, Parham; Lolak, Nebih; Işık, Mesut; Durgun, Mustafa; Budak, Yakup; Türkeş, Cüneyt; Gülçin, İlhami; Beydemir, Şükrü

A series of six N -carbamimidoyl-4-(3-substitutedphenylureido) benzenesulfonamide derivatives ( 2a-f ) were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives ( 2a-f ) 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-(3,4-dichlorophenyl)ureido) benzenesulfonamide ( 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-(3-chlorophenyl)ureido) benzenesulfonamide ( 2e ) showed strong a-GLY inhibitory effect, with K I values of 103.94 ± 13.06 nM. The antidiabetic effects of the novel synthesized compounds ( 2a-f ) 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.