RESUMEN
Two new lanthanide-complexes based on the 5-nitropicolinate ligand (5-npic) were obtained and fully characterized. Single-crystal X-ray diffraction revealed that these compounds are isostructural to a Dy-complex, previously published by us, based on dinuclear monomers link together with an extended hydrogen bond network, providing a final chemical formula of [Ln2(5-npic)6(H2O)4]·(H2O)2, where Ln = Dy (1), Gd (2), and Tb (3). Preliminary photoluminescent studies exhibited a ligand-centered emission for all complexes. The potential antitumoral activity of these materials was assayed in a prostatic cancer cell line (PC-3; the 2nd most common male cancerous disease), showing a significant anticancer activity (50-60% at 500 µg·mL-1). In turn, a high biocompatibility by both, the complexes and their precursors in human immunological HL-60 cells, was evidenced. In view of the strongest toxic effect in the tumoral cell line provided by the free 5-npic ligand (~ 40-50%), the overall anticancer complex performance seems to be triggered by the presence of this molecule.
Asunto(s)
Antineoplásicos , Elementos de la Serie de los Lantanoides , Ácidos Picolínicos , Humanos , Elementos de la Serie de los Lantanoides/química , Elementos de la Serie de los Lantanoides/farmacología , Ácidos Picolínicos/química , Ácidos Picolínicos/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Masculino , Ensayos de Selección de Medicamentos Antitumorales , Modelos Moleculares , Células HL-60 , Cristalografía por Rayos X , Estructura Molecular , Línea Celular Tumoral , Células PC-3 , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
Targeted protein degradation has emerged as an alternative therapy against cancer, offering several advantages over traditional inhibitors. The new degrader drugs provide different therapeutic strategies: they could cross the phospholipid bilayer membrane by the addition of specific moieties to extracellular proteins. On the other hand, they could efficiently improve the degradation process by the generation of a ternary complex structure of an E3 ligase. Herein, we review the current trends in the use of TAC-based technologies (TACnologies), such as PROteolysis TArgeting Chimeras (PROTAC), PHOtochemically TArgeting Chimeras (PHOTAC), CLIck-formed Proteolysis TArgeting Chimeras (CLIPTAC), AUtophagy TArgeting Chimeras (AUTAC), AuTophagosome TEthering Compounds (ATTEC), LYsosome-TArgeting Chimeras (LYTAC), and DeUBiquitinase TArgeting Chimeras (DUBTAC), in experimental development and their progress towards clinical applications.
RESUMEN
Bacteriophages are ubiquitous in nature and their use is a current promising alternative in biological control. Multidrug resistant (MDR) bacterial strains are present in the livestock industry and phages are attractive candidates to eliminate them and their biofilms. This alternative therapy also reduces the non-desirable effects produced by chemicals on food. The World Health Organization (WHO) estimates that around 420,000 people die due to a foodborne illness annually, suggesting that an improvement in food biocontrol is desirable. This review summarizes relevant studies of phage use in biocontrol focusing on treatments in live animals, plants, surfaces, foods, wastewaters and bioremediation.