title: Phenolic group on A-ring is key for dracoflavan B as a selective noncompetitive inhibitor of α-amylase.
abstract: A high throughput assay was applied to guide the isolation of a new pancreatic α-amylase inhibitor, dracoflavan B, from the dragon's blood resin from Daemonorops draco. Applying C18 column, we successfully isolated both diastereomers and their structures verified by (1)H NMR spectra in comparison with the literature values. Their activity in inhibition of pancreatic α-amylase with comparable IC50 values of 23μM (A type) and 27μM (B type) that are similar to that of acarbose. Dracoflavan B shows much weaker activity in inhibiting bacterial α-amylase and no activity towards fungal α-amylase. Moreover, both isomers show no inhibitory activity towards mammalian α-glucosidase. Kinetic analysis revealed that using starch as the substrate, dracoflavan B was a non-competitive α-amylase inhibitor with a Ki value of 11.7μM. Lack of α-amylase inhibition for proanthocyanidin A2 dimer demonstrated that dracoflavan B hydrophobic nature of the B, A', C' and B' rings are important for its α-amylase inhibition. In addition, selective chemical modification studies revealed that the phenolic group is also vital to dracoflavan B for its pancreatic α-amylase inhibition activity. Without the A ring phenolic hydrogen bond donor, the derivatives of dracoflavan B showed detrimental α-amylase inhibition. On the contrary, galloylation on the A ring phenolic OH group enhanced the activity as shown by the low IC50 (12μM) against α-amylase which is 56% more potent as compared to dracoflavan B.
authors.affiliation: Food Science and Technology Program, Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore.
authors.forename: Zhi Siang
authors.initials: ZS
authors.lastname: Toh
authors.affiliation: Food Science and Technology Program, Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Chemistry & Biological Chemistry, 50 Nanyang Ave., Singapore 639798, Republic of Singapore.
authors.forename: Yew Mun
authors.initials: YM
authors.lastname: Yip
authors.affiliation: Food Science and Technology Program, Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore.
authors.forename: Yuyun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Food Science and Technology Program, Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore.
authors.forename: Benedict Jeffrey Ang
authors.initials: BJ
authors.lastname: Lim
authors.affiliation: Division of Chemistry & Biological Chemistry, 50 Nanyang Ave., Singapore 639798, Republic of Singapore. Electronic address: ZHANGDW@ntu.edu.sg.
authors.forename: Daiwei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Food Science and Technology Program, Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore; National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu 215123, People's Republic of China. Electronic address: chmhdj@nus.edu.sg.
authors.forename: Dejian
authors.initials: D
authors.lastname: Huang
mesh_terms: D000818:Animals; D028023:Arecaceae / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D010179:Pancreas / Q000201:enzymology; D010636:Phenols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry*; D013552:Swine; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D000516:alpha-Amylases; C525191:dragon's blood
keywords: Daemonorops draco; Dracoflavan B; Proanthocyanidins; α-Amylase inhibitors