Photosensitizing properties and subcellular localisation of 3,4‑dihydro‑β‑carbolines harmaline and harmalol Denofrio, M. Paula Paredes Martínez, José Manuel Yañuk, Juan G. Girón González, María Dolores Salto González, Rafael Talavera Rodríguez, Eva María Crovetto González, Luis Cabrerizo, Franco M. 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. 2024-02-08T12:03:51Z 2024-02-08T12:03:51Z 2023 journal article Published version: Denofrio, M.P., Paredes, J.M., Yañuk, J.G. et al. Photosensitizing properties and subcellular localisation of 3,4-dihydro-β-carbolines harmaline and harmalol. Photochem Photobiol Sci 22, 487–501 (2023). https://doi.org/10.1007/s43630-022-00328-7 https://hdl.handle.net/10481/88731 10.1007/s43630-022-00328-7 eng open access