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

Harmaline (1) and harmalol (2) represent two 3,4-dihydro-beta-carboline (DH beta 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. [GRAPHICS] .

Automated summary

This study investigated the differences in photosensitizing properties, cellular uptake, and cyto- and phototoxicity of harmaline and harmalol. The data showed that harmaline primarily causes DNA oxidative damage, while harmalol induces single-strand breaks. Additionally, harmalol may cause single-strand breaks through a concerted hydrolytic attack. The structure of the compounds also affects their subcellular uptake and toxicity. These results are important for understanding the biological, biomedical, and pharmacological roles of these alkaloids.