title: Synthesis of furofuran lignans as antidiabetic agents simultaneously achieved by inhibiting α-glucosidase and free radical.
abstract: Furofuran lignans such as sesamin have been recognized as promising antidiabetic agents as they possess curative as well as preventive effects toward diabetes complications. However, to date the structure-activity relationship has not been investigated due to the lack of a practical synthetic route capable of producing diverse furofuran lignans. Herein, we first introduced a single-step synthesis of these compounds starting from samin (4). Reaction of samin with a variety of electron-rich phenolics under acidic conditions afforded a total of 23 diverse furofuran lignans. On examination their inhibitions against α-glucosidase and free radicals, lignans having a free hydroxy group showed considerably enhanced inhibition, compared with their corresponding starter 4 and related lignans sesamin (1) and sesamolin (3). In addition, the mechanism underlying the α-glucosidase inhibition of a particular active lignan (epi -6) was verified to be mixed manner between competitive and noncompetitive inhibition.
authors.affiliation: Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Wisuttaya
authors.initials: W
authors.lastname: Worawalai
authors.affiliation: Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Phonpimon
authors.initials: P
authors.lastname: Khongchai
authors.affiliation: Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Nantaporn
authors.initials: N
authors.lastname: Surachaitanawat
authors.affiliation: Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. preecha.p@chula.ac.th.
authors.forename: Preecha
authors.initials: P
authors.lastname: Phuwapraisirisan
mesh_terms: D000818:Animals; D004149:Dioxoles / Q000138:chemical synthesis* / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017705:Lignans / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D004149:Dioxoles; D005609:Free Radicals; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D017705:Lignans; C054124:sesamolin; D000520:alpha-Glucosidases; C054125:sesamin
keywords: Antioxidant; Diabetes; Friedel-Crafts; Glucosidase; Oxocarbenium; Sesamum indicum