title: Caffeoylquinic acid derivatives isolated from the aerial parts of Gynura divaricata and their yeast α-glucosidase and PTP1B inhibitory activity.
abstract: The phytochemical investigation of natural products of Gynura divaricata led to the isolation of eleven caffeoylquinic acid derivatives. They were characterized by spectrometric methods as 5-O-caffeoylquinic acid (1), 5-O-p-coumaroylquinic acid (2), 5-O-feruloylquinic acid (3), methyl 5-O-caffeoylquinate (4), 3,4-dicaffeoylquinic acid (5), 3,5-dicaffeoylquinic acid (6), 4,5-dicaffeoylquinic acid (7), methyl 3,4-dicaffeoylquinate (8), methyl 3,5-dicaffeoylquinate (9), methyl 4,5-dicaffeoylquinate (10) and ethyl 4,5-dicaffeoylquinate (11). The individual compounds were screened for the inhibition of yeast α-glucosidase and Protein Tyrosine Phosphatase 1B (PTP1B) using in vitro assays. Among the isolated compounds, 3,4-dicaffeoylquinic acid (5), 4,5-dicaffeoylquinic acid (7), methyl 3,4-dicaffeoylquinate (8) and methyl 4,5-dicaffeoylquinate (10) exhibited significant inhibitory activities against α-glucosidase. In addition, 5-O-p-coumaroylquinic acid (2), 3,5-dicaffeoylquinic acid (6) and 4,5-dicaffeoylquinic acid (7) had considerable inhibitory effect against PTP1B. Based on these findings, the caffeoylquinic acid derivatives were deduced to be potentially responsible for the anti-diabetic activity of G. divaricata. The preliminary structure-activity relationship study suggests that the number and positioning of caffeoyl groups in the quinic acid derivatives are important for both α-glucosidase and PTP1B inhibitory potency. Moreover, the corresponding methyl esters of some dicaffeoylquinic acids have enhanced inhibitory activity against yeast α-glucosidase.
authors.affiliation: Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China; Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, Ghent 9000, Belgium; Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, Ghent 9000, Belgium. Electronic address: Sven.Mangelinckx@UGent.be.
authors.forename: Sven
authors.initials: S
authors.lastname: Mangelinckx
authors.affiliation: Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China. Electronic address: lwlcnbg@mail.cnbg.net.
authors.forename: Weilin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, Ghent 9000, Belgium.
authors.forename: Norbert
authors.initials: N
authors.lastname: De Kimpe
mesh_terms: D019659:Asteraceae / Q000737:chemistry*; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry*; D015394:Molecular Structure; D035261:Plant Components, Aerial / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D002726:Chlorogenic Acid; D065089:Glycoside Hydrolase Inhibitors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D011801:Quinic Acid; D000520:alpha-Glucosidases; C472707:caffeoylquinic acid; C478100:3,4-di-O-caffeoylquinic acid; C100434:3,5-dicaffeoylquinic acid; C473200:5-caffeoylquinic acid
keywords: Anti-diabetic activity; Caffeoylquinic acid derivatives; Gynura divaricata