Potent Glucosidase Inhibitors: De-O-sulfonated Ponkoranol and Its Stereoisomer

被引:40
作者
Eskandari, Razieh [1 ]
Kuntz, Douglas A. [2 ,3 ]
Rose, David R. [2 ,3 ,4 ]
Pinto, B. Mario [1 ]
机构
[1] Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada
[3] Ontario Canc Inst, Div Mol & Struct Biol, Toronto, ON M5G 2M9, Canada
[4] Univ Waterloo, Dept Biol, Waterloo, ON N2L 3G1, Canada
关键词
MEDICINE SALACIA-RETICULATA; SULFONIUM SULFATE STRUCTURE; HUMAN MALTASE GLUCOAMYLASE; CHAIN-EXTENDED HOMOLOGS; GLYCOSIDASE INHIBITORS; TRADITIONAL MEDICINE; CONVERSION; KOTALANOL; REVISION;
D O I
10.1021/ol1004005
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Ponkoranol, a glucosidase inhibitor isolated from the plant Salacia reticulata, comprises a sulfonium ion with an internal sulfate counterion. An efficient synthetic route to de-O-sulfonated ponkoranol and its 5'-stereoisomer is reported, and it is shown that these compounds are potent glucosidase inhibitors that inhibit a key intestinal human glucosidase, the N-terminal catalytic domain of maltase glucoamylase, with K, values of 43 +/- 3 and 15 +/- 1 nM, respectively.
引用
收藏
页码:1632 / 1635
页数:4
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