N-Methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains

N-Methyl-β-carboline (βC) alkaloids, including normelinonine F (1b) and melinonine F (2b), have been found in a vast range of living species playing different biological, biomedical and/or pharmacological roles. Despite this, molecular bases of the mechanisms through which these alkaloids would exer...

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Detalles Bibliográficos
Autores principales: Denofrio, María Paula, Rasse Suriani, Federico Ariel Osvaldo, Paredes, Jose M., Fassetta, Federico, Crovetto, Luis, Girón, María D., Salto, Rafael, Epe, Bernd, Cabrerizo, Franco Martín
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Física
Química
alkaloids
normelinonine F
melinonine F
N-Methyl-β-carboline
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/146533
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-146533
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Física
Química
alkaloids
normelinonine F
melinonine F
N-Methyl-β-carboline
spellingShingle Física
Química
alkaloids
normelinonine F
melinonine F
N-Methyl-β-carboline
Denofrio, María Paula
Rasse Suriani, Federico Ariel Osvaldo
Paredes, Jose M.
Fassetta, Federico
Crovetto, Luis
Girón, María D.
Salto, Rafael
Epe, Bernd
Cabrerizo, Franco Martín
N-Methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
topic_facet Física
Química
alkaloids
normelinonine F
melinonine F
N-Methyl-β-carboline
description N-Methyl-β-carboline (βC) alkaloids, including normelinonine F (1b) and melinonine F (2b), have been found in a vast range of living species playing different biological, biomedical and/or pharmacological roles. Despite this, molecular bases of the mechanisms through which these alkaloids would exert their effect still remain unknown. Fundamental aspects including the photosensitizing properties and intracellular internalization of a selected group of N-methyl-βC alkaloids were investigated herein. Data reveal that methylation of the βC main ring enhances its photosensitizing properties either by increasing its binding affinity with DNA as a biomolecular target and/or by increasing its oxidation potential, in a structure-dependent manner. As a general rule, N(9)-substituted βCs showed the highest photosensitizing efficiency. With the exception of 2-methyl-harminium, all the N-methyl-βCs investigated herein induce a similar DNA photodamage profile, dominated largely by oxidized purines. This fact represents a distinctive behavior when comparing with N-unsubstituted-βCs. On the other hand, although all the investigated compounds might accumulate mainly into the mitochondria of HeLa cells, methylation provides a distinctive dynamic pattern for mitochondrial uptake. While rapid (passive) diffusion is most probably reponsible for the prompt uptake/release of neutral βCs, an active transport appears to mediate the (reatively slow) uptake of the quaternary cationic βCs. This might be a consequence of a distinctive subcellular localization (mitochondrial membrane and/or matrix) or interaction with intracellular components. Biomedical and biotechnological implications are also discussed herein.
format Articulo
Articulo
author Denofrio, María Paula
Rasse Suriani, Federico Ariel Osvaldo
Paredes, Jose M.
Fassetta, Federico
Crovetto, Luis
Girón, María D.
Salto, Rafael
Epe, Bernd
Cabrerizo, Franco Martín
author_facet Denofrio, María Paula
Rasse Suriani, Federico Ariel Osvaldo
Paredes, Jose M.
Fassetta, Federico
Crovetto, Luis
Girón, María D.
Salto, Rafael
Epe, Bernd
Cabrerizo, Franco Martín
author_sort Denofrio, María Paula
title N-Methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_short N-Methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_full N-Methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_fullStr N-Methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_full_unstemmed N-Methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_sort n-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/146533
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