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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
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Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
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Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible...
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The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the...
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Video Experimental Relacionado

Updated: Sep 10, 2025

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Los derivados de ridaifen funcionan como agentes lisosomotrópicos potentes, dependiendo de sus cadenas laterales

Yuta Semba1, Kyoka Komukai2, Eri Murata2

  • 1Division of Life Science and Engineering, College of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-machi, Hiki-gun, Saitama, 350-0394, Japan.

European journal of pharmacology
|August 22, 2025
PubMed
Resumen

Ridaifen-B (RID-B), un análogo del tamoxifeno, neutraliza los lisosomas, inhibiendo la autofagia y induciendo la muerte de las células cancerosas. Esta disfunción lisosómica ofrece una estrategia potencial para superar la resistencia a los medicamentos en el tratamiento del cáncer.

Palabras clave:
Compuesto anticancerígenoLa autofagiaAgentes lisosomotrópicosRidaifen y sus derivados

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Área de la Ciencia:

  • Biología celular
  • Oncología molecular
  • Descubrimiento de drogas

Sus antecedentes:

  • La autofagia es crucial para la homeostasis celular, pero su desregulación puede causar resistencia a la quimioterapia.
  • Los compuestos de Ridafen (RID), análogos del tamoxifeno, muestran una potente actividad anticancerígena y modulan la autofagia.

Objetivo del estudio:

  • Investigar la interacción de los compuestos RID con la autofagia e identificar los factores que contribuyen a su citotoxicidad.
  • Explorar el potencial de los derivados de RID en la superación de la resistencia a los medicamentos relacionados con la autofagia en el tratamiento del cáncer.

Principales métodos:

  • Síntesis de derivados RID con cadenas laterales básicas variables.
  • Evaluación de la viabilidad celular (ensayo MTT), del pH lisosomal (citometría de flujo) y de la distribución subcelular (compuesto conjugado con colorante fluorescente).
  • Monitoreo de marcadores autofágicos y apoptóticos a través de inmunoblotas y imágenes confocales.

Principales resultados:

  • RID-B neutralizó eficazmente los lisosomas, inhibiendo el flujo autofágico y llevando al estrés proteotóxico y la apoptosis.
  • Disfunción lisosómica inducida por la señalización apoptótica iniciada por RID-B, como lo demuestra la reducción de la apoptosis con el tratamiento con bafilomicina A1.
  • Se encontró una correlación entre el número de cadenas laterales básicas, la neutralización lisosómica y la citotoxicidad en los derivados de RID.

Conclusiones:

  • Las cadenas laterales básicas mejoran el comportamiento lisosomotrópico de los derivados de RID, promoviendo la inhibición de la autofagia y la apoptosis.
  • La neutralización lisosómica es un mecanismo clave subyacente a la mayor citotoxicidad de los compuestos RID.
  • Los análogos modificados de tamoxifeno como RID-B representan una estrategia prometedora para superar la resistencia a los medicamentos relacionados con la autofagia en el tratamiento del cáncer.