Deciphering Preferential Binding Interaction of Synthetic Pyrido[2,3‐c]Carbazole Alkaloid Derivative (PCAD) with Pu24T G‐quadruplex DNA

Abstract

AbstractG‐quadruplex DNA (GQ‐DNA) represents one of the most significant non‐canonical nucleic acid configurations. GQ‐DNA producing sequences are found in different important genomic areas, including the promoter islands of numerous oncogenes and human telomere regions. Therefore, GQ‐DNA is a key target for anticancer medicines. GQ‐DNA has a highly variable structure, it is critical to develop ligand molecules that selectively target certain quadruplex sequences. Natural products such as pyridocarbazole alkaloids have grown interest for healthcare and medicinal values and they considered as a valuable source of innovative anticancer medicines among the chemical compounds. In this investigation, we have synthesised and characterized pyrido[2,3‐c]carbazole derivative (PCAD) through NMR and IR spectra and explore the interactions between PCAD and Pu24T GQ (promoter region), h‐TELO GQ (telomere region) and duplex DNA by employing several multi‐spectroscopic analytical techniques. We have found that PCAD preferentially interacts with Pu24T GQ DNA as compared to other DNA sequences. These findings highlights PCAD as an appealing option for targeting the Pu24T promoter region and consequently acting as an anti‐cancer drug. This study also highlights the potential for developing drugs to understand the molecular aspects of GQ DNA recognition and signaling, paving the way for future research on GQ biology.