Tanabe, Genzoh, Xie, Weijia, Balakishan, Gorre, Amer, Mumen F.A., Tsutsui, Nozomi, Takemura, Haruka, Nakamura, Shinya, Akaki, Junji, Ninomiya, Kiyofumi, Morikawa, Toshio, Nakanishi, Isao, and Muraoka, Osamu
Using an in silico method, seven analogs bearing hydrophobic substituents ( 8a : Me, 8b : Et, 8c : n -Pent, 8d : n -Hept, 8e : n -Tridec, 8f : isoBu and 8g : neoPent) at the 3′-O-position in salacinol ( 1 ), a highly potent natural α-glucosidase inhibitor from Ayurvedic traditional medicine ‘ Salacia ’, were designed and synthesized. In order to verify the computational SAR assessments, their α-glucosidase inhibitory activities were evaluated in vitro . All analogs ( 8a – 8g ) exhibited an equal or considerably higher level of inhibitory activity against rat small intestinal α-glucosidases compared with the original sulfonate ( 1 ), and were as potent as or higher in potency than the clinically used anti-diabetics, voglibose, acarbose or miglitol. Their activities against human maltase exhibited good relationships to the results obtained with enzymes of rat origin. Among the designed compounds, the one with a 3′- O -neopentyl moiety ( 8g ) was most potent, with an approximately ten fold increase in activity against human maltase compared to 1 . [ABSTRACT FROM AUTHOR]