@misc{10481/63549,
year = {2020},
month = {7},
url = {http://hdl.handle.net/10481/63549},
abstract = {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.},
organization = {ANPCyT
	
PICT-2015-0374
2016-0370
2018-3193},
organization = {Spanish Ministry of Economy and Competitiveness 	
CTQ201785658-R
CTQ2014-55474-C2-2-R},
publisher = {Royal Society of Chemistry},
title = {N-Methyl-β-carboline alkaloids: structuredependent photosensitizing properties and localization in subcellular domains},
doi = {10.1039/d0ob01122c},
author = {Denofrio, M. Paula and Rasse-Suriani, Federico A. O. and Paredes Martínez, José Manuel and Fassetta, Federico and Crovetto González, Luis and Girón González, María Dolores and Salto González, Rafael and Epe, Bernd and Cabrerizo, Franco M.},
}