Molecular recognition of telomere DNA sequence by 2, 6 anthraquinone derivatives leads to thermal stabilization and induces apoptosis in cancer cells

According to current research, anti-cancer anthraquinones impact telomere disruption and may interact with G-quadruplex DNA that triggers signaling to apoptosis. The present study represents the biophysical investigation of oxidative stress, late apoptosis, and induced senescence among cancer cells after binding laboratory synthe-sized piperidine-based anthraquinone derivatives, 2, 6-Bis [(3-piperidino)acetamido)]anthracene-9,10-dione (N-1P) and 2, 6-Bis [piperidino)propionamido]anthracene-9,10-dione (N-2P), with G-quadruplex DNA. We employed biophysical approaches to explore the interaction of synthetic anthraquinone derivatives with quad-ruplex DNA sequences to influence biological activities in the presence of K+ and Na+ cations. The binding af-finity for N-2P and N-1P are Kb = 5.8 x 106 M-1 and Kb = 1.0 x 106 M-1, respectively, leading to hypo-/ hyper-chromism with 5-7 nm red shift and significant fluorescence quenching and changes in ellipticity resulting in external binding of both the ligands to G-quadruplex DNA. Ligand binding induced enhancement of ther-mostability of G4 DNA is greater in Na+ environment (& UDelta;Tm = 34 C) as compared to that in K+ environment (& UDelta;Tm = 21 C), thereby restricting telomerase binding access to telomeres. Microscopic images of treated cells indicated cellular shape, nuclear condensation, and fragmentation alterations. The findings pave the path for therapeutic research, given the great potential of modifying anthraquinone substituent groups towards improved efficacy, ROS generation, and G-quadruplex DNA selectivity.

Automated summary

This study investigated the interaction between laboratory synthesized piperidine-based anthraquinone derivatives (N-1P and N-2P) and G-quadruplex DNA, as well as their impact on oxidative stress, late apoptosis, and induced senescence in cancer cells. The results showed that these anthraquinone derivatives could bind to G-quadruplex DNA, leading to oxidative stress and cellular changes in cancer cells. The binding also increased the stability of G-quadruplex DNA, thereby restricting telomerase binding and potentially inhibiting cancer cell growth.