Synthesis of S-alkylated sulfonium-ions and their glucosidase inhibitory activities against recombinant human maltase glucoamylase.
The syntheses of nine S-alkylated, cyclic sulfonium-ions with varying alkyl chain lengths, as mimics of N-alkylated imino sugars, and their glucosidase inhibitory activities are described. The target compounds were synthesized by alkylation of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-d-arabinitol at the ring sulfur atom using various alkyl halides, followed by deprotection using boron trichloride. Enzyme inhibitory assays against recombinant human maltase glucoamylase (MGA), a critical enzyme in the small intestine involved in the breakdown of glucose oligosaccharides into glucose itself, shows that they are effective inhibitors of MGA with K(i) values ranging from 6 to 75 microM.
Mohan
Sankar
S
Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada V5A 1S6.
Sim
Lyann
L
Rose
David R
DR
Pinto
B Mario
BM
D000478:Alkylation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000378:metabolism; D013452:Sulfonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D013452:Sulfonium Compounds; D005959:Glucosidases; D000520:alpha-Glucosidases