ROS scavenging, DNA binding and NADPH oxidase inhibition potential of N’-Ferrocenylmethyl-N’- phenylpropionohydrazide using cyclic voltammetry and molecular docking

Abstract

Overactivation of the NOX results in an excess production of ROS, which is linked to oxidative stress and deoxyribonucleic acid (DNA) damage. Free radical formation is a physiological event mainly coming from cellular respiration. Inflammatory diseases, cardiovascular diseases, and cancer are only some illnesses that this could trigger. Therefore, chemicals that can block NADPH oxidase (NOX) are essential in maintaining a healthy level of oxidative stress. However, interacting with DNA can alter its shape and slow replication, protecting cells from death. In this study, cyclic voltammetry (CV) techniques were employed to assess the scavenging activity of N’-Ferrocenylmethyl-N’- phenylpropionohydrazide (NFPP) towards the superoxide anion radical (O2.−). Additionally, the DNA binding modes and binding free energies of NFPP were investigated. To support the experimental results, molecular docking was performed with DNA (PDB ID: 5VY6) and the enzyme NOX1 (PDB ID: 7CFZ). The results were consistent between the two approaches, showing that the chemical investigated had an IC50 lower than that of ascorbic acid (AA) and a spontaneous form of binding with (O2.−) and DNA due to the negative sign of binding energies. Minor groove binding with two conventional hydrogen bonds was the type of interaction with the DNA. The binding energy between NFPP and NADPH exhibited a significant correlation with the experimental findings, indicating a strong affinity and a reduced inhibition concentration compared to ascorbic acid.