N-Methyl-β-carboline alkaloids: structuredependent photosensitizing properties and localization in subcellular domains
Metadata
Show full item recordAuthor
Denofrio, M. Paula; Rasse-Suriani, Federico A. O.; Paredes Martínez, José Manuel; Fassetta, Federico; Crovetto González, Luis; Girón González, María Dolores; Salto González, Rafael; Epe, Bernd; Cabrerizo, Franco M.Editorial
Royal Society of Chemistry
Date
2020-07-01Referencia bibliográfica
Luis Crovetto, Franco M. Cabrerizo et al.. N-Methyl-β-carboline alkaloids: structuredependent photosensitizing properties and localization in subcellular domains. Org. Biomol. Chem., 2020, 18, 6519 [DOI: 10.1039/d0ob01122c]
Sponsorship
ANPCyT PICT-2015-0374 2016-0370 2018-3193; Spanish Ministry of Economy and Competitiveness CTQ201785658-R CTQ2014-55474-C2-2-RAbstract
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.