title: Probing the influence of carboxyalkyl groups on the molecular flexibility and the charge density of apigenin derivatives.
abstract: 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 ΔEHOMO-LUMO, which indicates the lowest stability and the highest inhibition activity. Graphical abstract Probing the influence of carboxyalkyl groups on the molecular flexibility and the charge density of apigenin derivatives.
authors.affiliation: Department of Chemical Engineering, Northwest University for Nationalities, Lanzhou, 730124, People's Republic of China. qiajiao@163.com.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Qi
authors.affiliation: Department of Life Sciences and Biological Engineering, Northwest University for Nationalities, Lanzhou, 730124, People's Republic of China.
authors.forename: H N
authors.initials: HN
authors.lastname: Lu
authors.affiliation: Department of Chemical Engineering, Northwest University for Nationalities, Lanzhou, 730124, People's Republic of China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Zhao
authors.affiliation: Gansu Province Computing Center, Lanzhou, 730000, People's Republic of China.
authors.forename: N Z
authors.initials: NZ
authors.lastname: Jin
keywords: Carboxyalkyl derivatives; Charge density distribution; Molecular docking; Quantum chemical calculations; α-glucosidase