Research Progress of Synthesis and Structure-activity Relationship Studies on Sulfonium-type α-glucosidase Inhibitors Isolated from Salacia Genus Plants

Weijia      Xie; Genzoh      Tanabe; Jinyi      Xu; Xiaoming      Wu; Toshio      Morikawa; Masayuki      Yoshikawa; Osamu      Muraoka

Abstract

Salacinol was isolated as the first naturally occurring sulfonium type α-glucosidase inhibitor from Salacia reticulata, a large woody, climbing plant widely distributed in Sri Lanka and South India, in 1997. This compound presents a quite unique zwitterionic sulfonium sulfate structure and its α-glucosidase inhibitory activity (in vitro) was revealed to be as potent as those of anti-diabetics used in clinic. Since then, great efforts have been made to discover other bioactive ingredients as potent α-glucosidase inhibitors from the same genus of plants, which directly led to the identification of several side chain analogs of salacinol such as kotalanol, salaprinol and ponkoranol together with their de-Osulfonated analogs. In the mean time, much attention has been focused on the total syntheses, structure activity relationship (SAR) studies on this group of natural products in order to design molecules with improved activities. Thus, as a possible result of present findings, this class of natural products has the potential to become lead compounds with potent α- glucosidase inhibitory activities, which could be further developed to a new class of hypoglycemic drug candidates. The present review was developed as a summary of the recent researches of total synthesis and SAR of this series of natural products. In addition, several important structural determinants including the most recent discoveries on SAR are summarized, which may provide new insights into the development of novel anti-diabetic agents.

Keywords: α-glucosidase inhibitor, anti-diabetics, computer-aided drug design, Salacia, SAR studies, Synthesis.

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