Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli, Estado de México, 54740, México.
Centro de Física Aplicada y Tecnología Avanzada, Universidad Nacional Autónoma de México, Boulevard Juriquilla, Querétaro, 76230, México.
Chem Biodivers. 2023 Mar;20(3):e202200554. doi: 10.1002/cbdv.202200554. Epub 2023 Feb 17.
The optimized geometry of palbociclib, (PD 0332991) (8-cyclopentyl-6-ethanoyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one), electrostatic potential map, molecular orbitals were calculated using the density functional theory. The geometry was used in a molecular docking study of palbociclib-kinase complexes, results could be explained by the charge of the nitrogen and oxygen atoms within the palbociclib. Energy gap of HOMO-LUMO surfaces, could help to explain the reactivity of the ligand and the hydrogen bonding with three different kinases, two of CDK6 and one of CDK4 type. Docking results are similar and complementary with literature reports using molecular dynamics, were hydrogen bonding was obtained and analyzed. The promiscuity of three kinases with palbociclib was detected by the docking results, thus, palbociclib could be used in other types of cancer besides myeloid leukemia. Some similarities are found with CDK4/CDK6 kinases which allow us to determine that palbociclib could be used to control other resistant inhibitor types of cancer.
帕博西尼（PD 0332991）（8-环戊基-6-乙酰基-5-甲基-2-（5-（哌嗪-1-基）吡啶-2-基氨基）吡啶并[2,3-d]嘧啶-7（8H）-酮）的优化几何形状、静电势图、分子轨道使用密度泛函理论计算。在帕博西尼-激酶复合物的分子对接研究中使用了该几何形状，结果可以用帕博西尼中氮和氧原子的电荷来解释。HOMO-LUMO 表面的能隙可以帮助解释配体的反应性和与三种不同激酶的氢键相互作用，其中两种为 CDK6，一种为 CDK4 型。对接结果与使用分子动力学获得和分析氢键的文献报道相似且互补。对接结果表明，三种激酶与帕博西尼的混杂性，因此，帕博西尼除了髓性白血病外，还可用于其他类型的癌症。与 CDK4/CDK6 激酶有一些相似之处，这使我们能够确定帕博西尼可用于控制其他耐药抑制剂类型的癌症。
