Antioxidant activity and inhibition of α-glucosidase by hydroxyl-functionalized 2-arylbenzo[b]furans.
This study synthesized a series of hydroxyl-functionalized 2-arylbenzo[b]furans based on the structure of tournefolic acid A and evaluated them for antioxidant and α-glucosidase inhibitory activities. Compounds 5a, 5e, and 5n showed remarkable inhibition of α-glucosidase (IC50 values of 1.9-3.0 μM), and they appear to be even more potent than quercetin. A kinetic binding study indicated that compounds 5a and 5n used a mechanism of mixed-competition to inhibit α-glucosidase. This study also revealed that compounds 5a and 5n bind to either the α-glucosidase or α-glucosidase-4-NPGP complex. Using the crystal structure of the Saccharomyces cerevisiae α-glucosidase, the molecular docking study has predicted the binding of compounds 5a and 5n to the active site of α-glucosidase through both hydrophobic and hydrogen interactions. A DPPH radical scavenging assay further showed that most hydroxyl-functionalized 2-arylbenzo[b]furans possess antioxidant activity. The exception was compound 5p, which has only one hydroxyl group on the 2-phenyl ring of 2-arylbenzo[b]furan. Our results indicate that hydroxyl-functionalized 2-arylbenzo[b]furans possess both antidiabetic as well as antioxidant properties.
Department of Food Science, Fu Jen Catholic University, Taipei 24205, Taiwan.
Jung-Feng
JF
Hsieh
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan.
Wei-Jen
WJ
Lin
Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
Kai-Fa
KF
Huang
Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
Jiahn-Haur
JH
Liao
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan.
Ming-Jaw
MJ
Don
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan.
Chien-Chang
CC
Shen
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan.
Young-Ji
YJ
Shiao
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan. Electronic address: wtli@nricm.edu.tw.
Wen-Tai
WT
Li
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020134:Catalytic Domain; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006878:Hydroxides / Q000737:chemistry*; D062105:Molecular Docking Simulation; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000737:chemistry / Q000378:metabolism*
D000975:Antioxidants; D001572:Benzofurans; D065089:Glycoside Hydrolase Inhibitors; D006878:Hydroxides; C031356:hydroxide ion; D000520:alpha-Glucosidases; C105430:benzofuran
Alpha-glucosidase; Antioxidant; DPPH radical scavenging assay; Hydroxyl-functionalized 2-arylbenzo[b]furans