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Synthesis of furofuran lignans as antidiabetic agents simultaneously achieved by inhibiting α-glucosidase and free radical

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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.

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Acknowledgments

This project was funded by the Thailand Research Fund (RSA5880027) and the Ratchadapisek Sompoch Endowment Fund, Chulalongkorn University (Sci-Super 2014–011). PK and NS are recipients of the Science Achievement Scholarship of Thailand (SAST). Chulalongkorn University Postdoctoral Fellowship to WW is acknowledged. We would also like to express our thanks to Dr. Rico Ramadhan for technical assistance in the kinetic study.

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Authors and Affiliations

  1. Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand

    Wisuttaya Worawalai, Phonpimon Khongchai, Nantaporn Surachaitanawat & Preecha Phuwapraisirisan

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  1. Wisuttaya Worawalai
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  2. Phonpimon Khongchai
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  3. Nantaporn Surachaitanawat
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  4. Preecha Phuwapraisirisan
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Correspondence to Preecha Phuwapraisirisan.

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Worawalai, W., Khongchai, P., Surachaitanawat, N. et al. Synthesis of furofuran lignans as antidiabetic agents simultaneously achieved by inhibiting α-glucosidase and free radical. Arch. Pharm. Res. 39, 1370–1381 (2016). https://doi.org/10.1007/s12272-016-0778-9

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