Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells

A set of arylazo sulfones, known to undergo N-S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probab...

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Published in:International journal of molecular sciences 2023-01, Vol.24 (3), p.1834
Main Authors: Mikra, Chrysoula, Mitrakas, Achilleas, Ghizzani, Virginia, Katsani, Katerina R, Koffa, Maria, Koukourakis, Michael, Psomas, George, Protti, Stefano, Fagnoni, Maurizio, Fylaktakidou, Konstantina C
Format: Article
Language:English
Subjects:
Cancer therapies
Cell death
Chemotherapy
Cleavage
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA Cleavage
DNA damage
Experiments
Fluorides
Humans
Light
Light effects
Melanoma
Molecular docking
Molecular Docking Simulation
Nitrogen
Photodynamic therapy
Radiation damage
Sulfones
Sulfones - pharmacology
Thymus gland
Tumor cell lines
Ultraviolet Rays
Viscosity
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Summary:A set of arylazo sulfones, known to undergo N-S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probably due to DNA intercalation) was analyzed by means of molecular docking "in silico" calculations that pointed out polar contacts, mainly via the sulfonyl moiety. Incubation with plasmid pBluescript KS II revealed DNA cleavage that has been studied over time and concentration. UV-A irradiation considerably improved DNA damage for most of the compounds, whereas under visible light the effect was slightly lower. Moving to in vitro experiments, irradiation was found to slightly enhance the death of the cells in the majority of the compounds. Naphthylazosulfone showed photo-disruptive effect under UV-A irradiation (IC ~13 μΜ) followed by derivatives and (IC ~100 μΜ). Those compounds were irradiated in the presence of two non-cancer cell lines and were found equally toxic only upon irradiation and not in the dark. The temporal and spatial control of light, therefore, might provide a chance for these novel scaffolds to be useful for the development of phototoxic pharmaceuticals.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24031834