红葱中小分子化合物对透明质酸酶的分子对接研究

Molecular Docking Study on the Interaction between Hyaluronidase and Small-molecule Compounds in Eleutherine americana

鸢尾科植物红葱是我国西南地区民间药用植物。由于红葱化学成分分离纯化及鉴定方面的原因,妨碍了红葱药理学研究的深入。本文基于文献收集到的已知化学结构的39种红葱化学成分,利用分子模拟对接软件Auto Dock 4.2,以分子对接结合自由能为标准,评价红葱化学成分与透明质酸酶(HAase)间的相互作用,从中筛选出HAase抑制剂,同时采用Elson-Morgan改良法测定红葱不同极性提取物对HAase活性的影响。实验中筛选出10个与HAase结合较好的化合物,其中化合物37,33的对接结合能最低,分别为-7.73和-7.72 kcal/mol,提示其可能具有较强的HAase抑制活性。实验结果显示HAase分子中氨基酸残基TYR75、ASN37和GLU131是化合物与酶形成氢键的重要作用位点。酶活性测定实验显示红葱不同极性提取物对HAase有一定的抑制作用。本研究结果为进一步探讨红葱化学成分对HAase活性的影响提供了参考依据。

Eleutherine americana is a folk medicinal plant common in Southwest China. Issues of isolation, purification, and identification of chemical constituents of Eleutherine americana have limited an in-depth study of its pharmacology. In this study, based on the 39 known chemical components of Eleutherine americana described in the literature, the interaction between hyaluronidase（HAase） and the chemical constituents of Eleutherine americana was evaluated using the molecular docking simulation software Auto Dock4.2, using the binding free energy in molecular docking as the standard. HAase inhibitors were selected, and the effects of Eleutherine americana extracts with different polarities on HAase activity were also determined with a modified Elson-Morgan method. Ten compounds that were predicted to have good binding with HAase were screened out. Among them, compounds 37 and 33 had the lowest binding free energies, at-7.73 and-7.72 kcal/mol, respectively, implying a good inhibitory effect on HAase activity. The experimental results showed that amino acid residues TYR75, ASN37, and GLU131 of HAase were critical reactive sites responsible for the formation of hydrogen bonds between compounds and HAase. The enzyme activity results also showed that extracts of Eleutherine americana with different polarities had different inhibitory effects on HAase. This study provides a reference basis for a further exploration of the effects of the chemical constituents in Eleutherine americana on HAase activity.