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

Abstract

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 1 showed photo-disruptive effect under UV-A irradiation (IC50 ~13 μΜ) followed by derivatives 14 and 17 (IC50 ~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.

Arylazo sulfones: multifaceted photochemical reagents and beyond

“…The experimental results clearly indicated that the synthesized arylazo sulfones can be used as phototoxic pharmaceuticals for cancer treatment (Scheme 40). 68…”

An Efficient Approach for the Synthesis and Antitumor Evaluation of Novel Azo‐ and Anil‐Linked with 3‐Aminopyrazolo[3,4‐b]pyridine

“…[14][15][16] In addition, iminopyrazole, pyrimidoquinoline derivatives, and pyridopyrazolpyrimidines are significant molecules that have gained a considerable amount of attention due to their wide variety of industrial and biomedical applications, including antitumor, [17,18] antibacterial, [19,20] antioxidant, [19] antifungal, [20,21] antimalarial, [22] anti-inflammatory, [23,24] antiviral, [18] and an azo derivative that is effective in DNA cleaving. [25] Additionally, imines have been discovered to have cytotoxic and antiproliferative activity against some cancer cell lines, including (Panc-1), (Caco-2), and leukemia, [26,27] in which the azomethine link was thought to be vital for biological activity. [28,29] Herein, we introduce an efficient method for synthesizing an azo-and anil-linked with 3-aminopyrazolo [3,4-b]pyridine derivatives and tested their cytotoxic activity against the A2780CP, MCF-7, and HepG-2 cell lines.…”

Frontiers in New Drug Discovery: From Molecular Targets to Preclinical Trials

“…Two articles consider the creation of phototoxic compounds and methods of photodynamic cancer therapy. Mikra et al [3] synthesized a set of arylazo sulfones, known to undergo N-S bond cleavage upon exposure to light, and investigated their activity in the dark and upon the irradiation of DNA. It turned out that exposure to UV light leads to structural rearrangements in some arylazo sulfones, increasing their cytotoxic activity against several cell lines.…”