Decoding the Potential of HRAS2 i‐Motif DNA Promoter to Become a Pinpoint Target by Phytomedicine Naringenin

Abstract Cytosine‐rich i‐motif (iM) DNA tetraplexes can influence oncogenic transcription and developing phytomedicines for iMs is a viable approach for cancer and other disease treatments. Although natural compounds have been studied as iM binding ligands for anticancer drug discovery, research on the structure‐interaction link between iM and ligand, like the influence of noncoplanar configurations on iM‐ligand binding, is rarely explored. Naringenin (NAR) have gained attention for their potential medicinal properties including high potency and minimal cytotoxicity. Our extensive biophysical and thermodynamic investigations have revealed that NAR interacted preferentially with HRAS2 iM compared to other experimental iMs. This research indicates that it is feasible to regulate gene expression by targeting HRAS2 iM with NAR, which might be beneficial in the development of anticancer medicines. The novel mechanical characteristics of NAR for HRAS2 iM may be important in disease treatments, providing critical insights for the future discovery of drugs with unique therapeutic attributes.