PDF(Pubmed)
Abstract：
A theoretical analysis of the potential inhibition of human sucrase-isomaltase (SI) by flavonoids was carried out with the aim of identifying potential candidates for an alternative treatment of type 2 diabetes. Two compounds from maize silks, maysin and luteolin, were selected to be studied with the structure-based density functional theory (DFT), molecular docking (MDock), and molecular dynamics (MD) approaches. The docking score and MD simulations suggested that the compounds maysin and luteolin presented higher binding affinities in N-terminal sucrase-isomaltase (NtSI) than in C-terminal sucrase-isomaltase (CtSI). The reactivity parameters, such as chemical hardness (η) and chemical potential (µ), of the ligands, as well as of the active site amino acids of the NtSI, were calculated by the meta-GGA M06 functional in combination with the 6-31G(d) basis set. The lower value of chemical hardness calculated for the maysin molecule indicated that this might interact more easily with the active site of NtSI, in comparison with the values of the acarbose and luteolin structures. Additionally, a possible oxidative process was proposed through the quantum chemical calculations of the electronic charge transfer values (∆N) between the active site amino acids of the NtSI and the ligands. In addition, maysin displayed a higher ability to generate more oxidative damage in the NtSI active site. Our results suggest that maysin and luteolin can be used to develop novel α-glucosidase inhibitors via NtSI inhibition.
摘要：
进行了黄酮类化合物对人蔗糖酶-异麦芽糖酶（SI）的潜在抑制作用的理论分析，目的是鉴定2型糖尿病替代治疗的潜在候选者。两种来自玉米丝的化合物，美素和木犀草素,选择用基于结构的密度泛函理论(DFT)进行研究，分子对接（MDock），和分子动力学(MD)方法。对接得分和MD模拟表明，化合物美素和木犀草素在N端蔗糖酶-异麦芽糖酸酶（NtSI）中的结合亲和力高于C端蔗糖酶-异麦芽糖酸酶（CtSI）。反应性参数，如化学硬度(η)和化学势(µ)，配体，以及NtSI的活性位点氨基酸，通过meta-GGAM06功能结合6-31G(d)基集计算。为美素分子计算的较低的化学硬度值表明，这可能更容易与NtSI的活性位点相互作用，与阿卡波糖和木犀草素结构的值相比。此外,通过对NtSI活性位点氨基酸与配体之间的电子电荷转移值（ΔN）的量子化学计算，提出了可能的氧化过程。此外,Maysin在NtSI活性位点表现出更高的氧化损伤能力。我们的结果表明，可以通过抑制NtSI来开发新型的α-葡萄糖苷酶抑制剂。
