Nucleobase Level Information into the Folding of G-Quadruplex by Anti-inflammatory Drugs in the Absence of Salt.

G-quadruplexes (G4s) in the telomere region are important targets for cancer therapy. Molecules that can fold and stabilize the telomere DNA sequences, even in the absence of salt, can be an exciting prospect for therapy purposes. Anti-inflammatory drugs hydroxychloroquine (HCQ) and chloroquine (CQ) have shown promising effects in cancer therapy and also in the different levels of trial stages. In this study, we have investigated the structure and stability of several natural and mutated telomeric sequences with anti-inflammatory drugs and their analogues in the absence of salts using the biophysical and docking methods to understand the role of the quartet and loop nucleobases of DNA along with the functional group of drugs responsible for triggering the folding of telomeric DNA sequences into G4. The findings indicate that the hydrogen bonding between the charged side chain with the guanine repeating unit associated with the quartet and the thymine in the terminal loops of telomere DNA is the main driving force for the folding of telomere DNA sequences into G4 induced by anti-inflammatory drugs. The data indicate that the adenine nucleobase in the loop of the telomere does not play any role in its folding process induced by HCQ and CQ.