Role of the thiosugar ring in the inhibitory activity of salacinol, a potent natural α-glucosidase inhibitor

Herein, ring-cleaved ( 24 ) and truncated ( 25 ) analogues of an azasugar, 1-deoxynojirimycin ( 23 ), exhibited inhibitory activity ( K i = 4-10 μM) equal to that of the parent compound ( 1 , K i = 14 μM). Based on this structure-activity relationship (SAR), four ring-cleaved ( 26a-26c and 27c ) and three truncated ( 28a-28c ) analogues of salacinol ( 1 ), a potent thiosugar-ring-containing α-glucosidase inhibitor, were synthesised. Bioassay results revealed that all the synthetics were inactive, indicating that the 5-membered thiosugar ring of 1 played an essential role in the potent activities of sulfonium-type inhibitors. The present findings are interesting and important in understanding the function of salacinol, considering that the observed inhibitory activity trend was contrary to the SAR observed in aza-compounds ( 23 , 24 , and 25 ) in a previous study, which suggested that the cyclic structure did not contribute to their strong inhibitory activity. In contrast to previous SAR studies of aza-compounds ( 23 vs. 24 and 25 ), the present study using analogues ( 26a-26c , 27c , and 28a-28c ) of salacinol ( 1 ) revealed an essential role of the thiosugar ring in effectively inhibiting α-glucosidase.