Photosensitizing properties and subcellular localisation of 3, 4-dihydro-β-carbolines harmaline and harmalol

Authors:

M. Paula Denofrio, Jose M. Paredes, Juan G. Yañuk, Maria D. Giron, Rafael Salto, Eva M. Talavera, Luis Crovetto & Franco M. Cabrerizo

Keywords:

Phototoxicity, extra cellular DNA photodamage, Co-localisation

Abstract:

Harmaline (1) and harmalol (2) represent two 3,4-dihydro-β-carboline (DHβCs) 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.

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