REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
J Enzyme Inhib Med Chem. 2011 Dec;26(6):755-66. doi: 10.3109/14756366.2010.549089. Epub 2011 Feb 1.
Quantitative structure activity relationship analysis was performed on a series of xanthone derivatives to establish the structural features required for α-glucosidase inhibitory activity. The computational and statistical analysis was performed with V life MDS (Molecular Design Suite) and Statistica software. The selected models show significant predictive power, stability, and reliability in terms of cross-validated correlation coefficient (Q(2)(cv) > 0.74 and Q(2)(test) > 0.5) and other validation parameters. The results show that the SaaaC count, MMFF_6 and dipole moment are mainly contributed for the activity along with the hydrophobicity descriptors. It describes that heteroatoms (oxygen atom connected with carbon atom) in the molecules are favourable for α-glucosidase inhibitory activity. The E-state count descriptor suggests that when carbon atoms connected with three aromatic bonds and hydrogen or other atoms are favourable for the activity. The SAHA and SAMH descriptors show that the hydrophilic area in the molecule is important for the activity while high hydrophilicity is unfavourable for the activity. This study concluded that hydrophilic, polar and/or electron negative groups, which are responsible for hydrogen bonding and interaction with the enzyme for favourable activity.
采用 V life MDS（分子设计套件）和 Statistica 软件对一系列紫檀烷衍生物进行定量构效关系分析，以确定抑制α-葡萄糖苷酶活性所需的结构特征。所选模型在交叉验证相关系数（Q(2)(cv)＞0.74 和 Q(2)(test)＞0.5）和其他验证参数方面表现出显著的预测能力、稳定性和可靠性。结果表明，SaaaC 计数、MMFF_6 和偶极矩主要与疏水性描述符一起对活性有贡献。这表明分子中的杂原子（与碳原子相连的氧原子）有利于α-葡萄糖苷酶抑制活性。E-state 计数描述符表明，当碳原子与三个芳环键和氢或其他原子相连时，有利于活性。SAHA 和 SAMH 描述符表明，分子中的亲水区对于活性很重要，而高亲水性不利于活性。本研究得出结论，亲水性、极性和/或带负电的基团，负责氢键形成和与酶相互作用，从而有利于活性。
