Synthesis and α-glucosidase inhibitory mechanisms of bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, a potential marine bromophenol α-glucosidase inhibitor.
Synthesis and α-glucosidase inhibitory mechanisms of bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, a potential marine bromophenol α-glucosidase inhibitor.
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作者：
Liu M;Zhang W;Wei J;Lin X
双(2,3-二溴-4,5-二羟基苄基)醚 (BDDE) 源自海藻，是一种潜在的 α-葡萄糖苷酶抑制剂，可用于治疗 2 型糖尿病。在本研究中，建立了一条合成路线作为获得 BDDE 的有效方法。采用荧光光谱、圆二色光谱和分子对接方法阐明了BDDE对α-葡萄糖苷酶的抑制机制。结果表明，采用所建立的合成方法可以有效且高效地制备BDDE。合成的 BDDE 与 α-葡萄糖苷酶结合并诱导酶发生微小的构象变化。对接结果表明BDDE和α-葡萄糖苷酶之间的相互作用是由疏水力和氢键驱动的。对接的BDDE分子完全埋入α-葡萄糖苷酶结合袋中，部分分子到达催化中心并与葡萄糖的位置重叠，其余分子向蛋白质表面延伸。这项研究为了解 BDDE-α-葡萄糖苷酶相互作用和开发新型 α-葡萄糖苷酶抑制剂提供了有用的信息。
Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE), derived from the marine algae, is a potential α-glucosidase inhibitor for type 2 diabetes treatment. In the present study, a synthetic route was established as a valid approach to obtain BDDE. Fluorescence spectra, circular dichroism spectra and molecular docking methods were employed to elucidate the inhibitory mechanisms of BDDE against α-glucosidase. The results showed that BDDE could be prepared effectively and efficiently with the established synthetic methods. Synthetic BDDE bound with α-glucosidase and induced minor conformational changes of the enzyme. The docking results indicated the interaction between BDDE and α-glucosidase was driven by both hydrophobic forces and hydrogen bonds. The docked BDDE molecule was completely buried in the α-glucosidase binding pocket with part of the molecule reaching the catalytic center and overlapping with the position of glucose, and the rest of the molecule extending towards protein surface. This study provides useful information for the understanding of the BDDE-α-glucosidase interaction and for the development of novel α-glucosidase inhibitors.
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