Probing the influence of carboxyalkyl groups on the molecular flexibility and the charge density of apigenin derivatives

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• 作者：Y. J. Qi ; H. N. Lu ; Y. M. Zhao ; N. Z. Jin
• 关键词：α ; glucosidase ; Carboxyalkyl derivatives ; Charge density distribution ; Molecular docking ; Quantum chemical calculations
• 刊名：Journal of Molecular Modeling
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：23
• 期：3
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Computer Applications in Chemistry; Molecular Medicine; Computer Appl. in Life Sciences; Characterization and Evaluation of Materials; Theoretical and Computational Chemistry;
• 出版者：Springer Berlin Heidelberg
• ISSN：0948-5023
• 卷排序：23

文摘

Apigenin is an important flavonoids due to its antidiabetic bioactivity. It was reported experimentally that the 7-substituent derivative of apigenin has higher biological activity than 4′- and 5-substituted derivatives while introducing sole carboxyalkyl group -(CH₂)₇COOH into the parent structure. Molecular docking studies indicated that the other two derivatives have lower binding affinities than the 7-substituent derivative (-7.52 kcal mol−1), which is considered to be a better inhibitor than the parent molecule. Almost all of the carbon atoms and oxygen atoms are coplaner for all three molecules in solution phase, however, all carboxyalkyl groups bend inside into the parent molecules in the active site, and the jagged geometries of the carbon chains are destroyed correspondingly. In addition, most of the electron densities of the chemical bonds for all molecules are decreased, especially the 7-substituent derivative. In contrast, most of the Laplacian values for three molecules are increased in the active site, which suggests that the charge densities at the bond critical point (bcp) are much more depleted than the solution phase. Dipole moments of derivatives are all increased in the active site, suggesting strong intermolecular interactions. After interacting with the S. cerevisiae α-glucosidase, only the 7-substituent derivative has the lowest energy gap ΔE_HOMO-LUMO, which indicates the lowest stability and the highest inhibition activity.