info:eu-repo/semantics/article
N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
Fecha
2020-07Registro en:
Denofrio, Maria Paula; Rasse Suriani, Federico Ariel Osvaldo; Paredes, Jose M.; Fassetta, Federico; Crovetto, Luis; et al.; N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 33; 7-2020; 1-12
1477-0520
CONICET Digital
CONICET
Autor
Denofrio, Maria Paula
Rasse Suriani, Federico Ariel Osvaldo
Paredes, Jose M.
Fassetta, Federico
Crovetto, Luis
Giron, Maria D.
Salto, Rafael
Epe, Bernd
Cabrerizo, Franco Martín
Resumen
N-methyl-Beta-carboline (bC) alkaloids, including normelinonine F and melinonine F, 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-bC alkaloids were investigated herein. Data reveal that methylation of the bC main ring enhances its photosensitizing properties either by increasing its binding affinity with DNA as biomolecular target and/or by increasing its oxidation potential, in a structure dependent manner. As a general rule, N(9)-substituted bCs showed the highest photosensitizing efficiency. With the exception of 2-methyl-harminium, all the N-methyl-bCs investigated herein induce a similar DNA photodamage profile, dominated largely by oxidized purines. This fact represents a distinctive behavior when comparing with N-unsubstituted-bCs. 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 bCs, an active transport appears to mediate the (reatively slow) uptake of the quaternary cationic bCs. 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.