Photosensitizing properties and subcellular localisation of 3,4-dihydro-β-carbolines harmaline and harmalol
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Published:2022-11-19
Issue:3
Volume:22
Page:487-501
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ISSN:1474-9092
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Container-title:Photochemical & Photobiological Sciences
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language:en
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Short-container-title:Photochem Photobiol Sci
Author:
Denofrio M. Paula, Paredes Jose M., Yañuk Juan G., Giron Maria D., Salto Rafael, Talavera Eva M., Crovetto Luis, Cabrerizo Franco M.ORCID
Abstract
AbstractHarmaline (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.
Graphical abstract
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.
Funder
ANPCyT Ministerio de Economía y Competitividad Universidad de Granada
Publisher
Springer Science and Business Media LLC
Subject
Physical and Theoretical Chemistry
Reference52 articles.
1. Zayed, R., & Wink, M. (2005). I2-Carboline and quinoline alkaloids in root cultures and intact plants of Peganum harmala, Zeitschrift fur Naturforschung - Section C. Journal of Biosciences, 60, 451–458. 2. Wang, Y. H., Samoylenko, V., Tekwani, B. L., Khan, I. A., Miller, L. S., Chaurasiya, N. D., Rahman, M. M., Tripathi, L. M., Khan, S. I., Joshi, V. C., Wigger, F. T., & Muhammad, I. (2010). Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson’s disease. Journal of Ethnopharmacology, 128, 662–671. 3. Stachell, S. J., Stockwell, S. A., & Van Vranken, D. L. (1999). The fluorescence of scorpions and cataractogenesis. Chemistry Biology, 6, 531–539. 4. Liu, C., Masuno, M. N., MacMillan, J. B., & Molinski, T. F. (2004). Enantioselective Total Synthesis of (+)-Milnamide A and Evidence of Its Autoxidation to (+)-Milnamide D. Angewandte Chemie International Edition, 43, 5951–5954. 5. Cao, N., & Wang, C. H. (2021). Strictosidine synthase, an indispensable enzyme involved in the biosynthesis of terpenoid indole and β-carboline alkaloids, Chin. Journal of Nature Medicines, 19, 591–607.
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