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

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

Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 2023 Mar

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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. 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. © 2022. The Author(s).

Citation

M Paula Denofrio, Jose M Paredes, Juan G Yañuk, Maria D Giron, Rafael Salto, Eva M Talavera, Luis Crovetto, Franco M Cabrerizo. Photosensitizing properties and subcellular localisation of 3,4-dihydro-β-carbolines harmaline and harmalol. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology. 2023 Mar;22(3):487-501