Prediction of the Binding Affinity between Fenoterol Derivatives and the b2 Adrenergic Receptor Using Atom-Based 3D-Chiral LinearIndices

  1. Castillo Garit, Juan A.
  2. García Domenech, Ramón
  3. Marrero Ponce, Yiovani
  4. Torrens Zaragozá, Francisco
  5. Abad Mazarío, Concepción
Revista:
Nereis: revista iberoamericana interdisciplinar de métodos, modelización y simulación

ISSN: 1888-8550

Año de publicación: 2012

Número: 4

Páginas: 9-18

Tipo: Artículo

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Otras publicaciones en: Nereis: revista iberoamericana interdisciplinar de métodos, modelización y simulación

Resumen

Los índices lineales 3D-quirales no-estocásticos y estocásticos basados en relaciones de átomos son aplicados al estudio del efecto agonista (afinidad de unión) sobre el receptor adrenérgico β2 (β2 -AR) entre una serie de 26 estereoisómeros del fenoterol, a los cuales se les ha reportado esta actividad. Una regresión lineal múltiple es llevada a cabo para predecir la afinidad de unión β2 -AR de los estereoisómeros. Se obtienen dos modelos QSAR estadísticamente significativos, capaces de describir más del 92 % de la varianza experimental de las afinidades de unión, empleando los índices lineales 3D-quirales no-estocásticos (R2 = 0.924 y s = 0.21) y estocásticos (R2 = 0.92 y s = 0.22) respectivamente. El poder predictivo y la robustez de los modelos obtenidos (comprobados mediante una validación cruzada dejando-uno-fuera) alcanzan valores de q2 = 0.893 (scv = 0.237) y q2 = 0.886 (scv = 0.245), correspondientemente. Los resultados obtenidos con nuestro enfoque fueron ligeramente superiores a aquellos resultados obtenidos previamente con un modelo 3D-QSAR, empleando el método CoMFA (R2 = 0.920, q2 = 0.847 y scv = 0.309). Los resultados de nuestro trabajo demuestran la utilidad de nuestro enfoque topológico para el descubrimiento de nuevos compuestos líderes candidatos a fármacos, incluso para estudios en los cuales las conformaciones tridimensionales de los compuestos juegan un rol fundamental en la actividad biológica.

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