Science and Technology Production
Article
Authorship
DENOFRIO, MARIA PAULA
;
Paredes, Jose M.
;
Yañuk, Juan Gabriel
;
Giron, Maria D.
;
Salto, Rafael
;
Talavera, Eva M.
;
Crovetto, Luis
;
CABRERIZO, FRANCO MARTIN
Date
2022
Publishing House and Editing Place
ROYAL SOC CHEMISTRY
Magazine
Photochemical and Photobiological Sciences,
vol. 22
(pp. 487-501)
ROYAL SOC CHEMISTRY
Summary
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SIGEVA
Harmaline (1) and harmalol (2) represent two 3,4-dihydro-?-carboline (DH?Cs) most frequently reported in a vast number of living systems. Fundamental aspects including the photosensitizing properties, cellular uptake, as well as the cyto- and phototoxicity of 1 and 2 were investigated herein. The molecular basis underlying the investigated processes are elucidated. Data reveal that both alkaloids show a distinctive pattern of extracellular DNA photodamage. Compound 1 induces a DNA photodamage p...
Harmaline (1) and harmalol (2) represent two 3,4-dihydro-?-carboline (DH?Cs) most frequently reported in a vast number of living systems. Fundamental aspects including the photosensitizing properties, cellular uptake, as well as the cyto- and phototoxicity of 1 and 2 were investigated herein. The molecular basis underlying the investigated processes are elucidated. Data reveal that both alkaloids show a distinctive pattern of extracellular DNA photodamage. Compound 1 induces a DNA photodamage profile dominated by oxidised purines and sites of base loss (AP sites), whereas 2 mostly induces single-strand breaks (SSBs) in addition to a small extent of purine oxidative damage. In both cases, DNA oxidative damage would occur through type I mechanism. In addition, a concerted hydrolytic attack is suggested as an extra mechanism accounting for the SSBs formation photoinduced by 2. Subcellular internalisation, cyto- and phototoxicity of 1 and 2 and the corresponding full-aromatic derivatives harmine (3) and harmol (4) also showed quite distinctive patterns in a structure-dependent manner. These results are discussed in the framework of the potential biological, biomedical and/or pharmacological roles reported for these alkaloids. Graphical abstract: [Figure not available: see fulltext.] The subtle structural difference (i.e., the exchange of a methoxy group for a hydroxyl substituent at C(7)) between harmaline and harmalol, gives rise to distinctive photosensitizing and subcellular localisation patterns.
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Key Words
DNA DAMAGELYSOSOMESCELLULAR UPTAKEHARMOLALKALOIDSHARMINEPHOTOTOXICITYENDOPLASMIC RETICULUMPARTIALLY HYDROGENATED ?-CARBOLINE
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