Phenolic group on A-ring is key for dracoflavan B as a selective noncompetitive inhibitor of α-amylase

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• 作者：Zhi Siang Toh^a ; ^&dagger ; ; Hongyu Wang^a ; ^&dagger ; ; Yew Mun Yip^b ; Yuyun Lu^a ; Benedict Jeffrey Ang Lim^a ; Daiwei Zhang^b ; ^{ZHANGDW@ntu.edu.sg" class="auth_mail" title="E-mail the corresponding author} ; Dejian Huang^a ; ^c ; ^{chmhdj@nus.edu.sg" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dracoflavan B ; α-Amylase inhibitors ; Daemonorops draco ; Proanthocyanidins
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2015
• 出版时间：15 December 2015
• 年：2015
• 卷：23
• 期：24
• 页码：7641-7649
• 全文大小：1808 K

文摘

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 ¹H NMR spectra in comparison with the literature values. Their activity in inhibition of pancreatic α-amylase with comparable IC₅₀ values of 23 μM (A type) and 27 μM (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 K_i value of 11.7 μM. 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 (12 μM) against α-amylase which is 56% more potent as compared to dracoflavan B.