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Desarrollo de Fármacos

Murillo Orsatto Haas1, Francielli Alana Pereira2, Drielli Rhiane Peres Colhado Arêas2

  • 1Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Nuevos derivados de terpenoides muestran promesa para el tratamiento de la enfermedad de Alzheimer. Estos compuestos naturales exhiben efectos neuroprotectores contra insultos oxidativos, inflamatorios y excitotóxicos en células del sistema nervioso central, sugiriendo un enfoque de terapia multitarget.

Palabras clave:
terpenoidesenfermedad de Alzheimerneuroprotecciónterapia multitargetderivados naturales

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Área de la Ciencia:

  • Neurociencia
  • Farmacología
  • Química de Productos Naturales

Sus antecedentes:

  • La enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo progresivo que causa demencia en todo el mundo.
  • La complejidad de la EA implica insultos sinérgicos a las células y estructuras del sistema nervioso central (SNC), lo que conduce al deterioro cognitivo.
  • Se buscan terapias multitarget utilizando compuestos naturales para la EA.

Objetivo del estudio:

  • Evaluar derivados de terpenoides de la familia Asteraceae para la posible terapia de la enfermedad de Alzheimer.
  • Evaluar propiedades similares a los fármacos, incluida la permeabilidad de la barrera hematoencefálica (BHE) y la biodisponibilidad oral.
  • Determinar la citotoxicidad y los efectos citoprotectores contra los insultos del SNC.

Principales métodos:

  • Análisis in silico utilizando SwissADME y ADMETLab 3.0 para propiedades similares a los fármacos.
  • Ensayos de citotoxicidad en células VERO, HT22 (neuronas del hipocampo) y C6-astrogliales.
  • Evaluación de la capacidad citoprotectora contra insultos inflamatorios, oxidativos y glutamatérgicos en neuronas y células gliales.

Principales resultados:

  • Dos de cinco compuestos mostraron potencial de permeabilidad de la BHE; tres tuvieron potencial de alta absorción gastrointestinal.
  • Todos los compuestos exhibieron baja citotoxicidad con valores de IC₅₀ >50 µM.
  • Los compuestos demostraron una protección significativa contra insultos inflamatorios (a 6,25 µM), oxidativos (a 3,125 µM) y glutamatérgicos (a 3,125 µM).

Conclusiones:

  • Los derivados de terpenoides poseen propiedades farmacológicas favorables, incluida la permeabilidad de la BHE y la biodisponibilidad oral.
  • Los compuestos muestran baja toxicidad y efectos neuroprotectores significativos contra múltiples insultos relevantes para la EA.
  • Estos compuestos naturales ofrecen una base prometedora para la terapia multitarget de la enfermedad de Alzheimer con una amplia ventana terapéutica.