Redox behavior of amsacrine: a pathway to understanding its biological action

Abstract

Investigating the redox characteristics of the anticancer agent Amsacrine (AMS) is crucial for understanding its biological activity and interactions with key biomolecules. A comprehensive electrochemical study was performed using cyclic, differential pulse, and square-wave voltammetry at a glassy carbon electrode (GCE). The effects of pH and scan rate were thoroughly examined. Results show that AMS undergoes independent oxidation and reduction processes. Its oxidation involves two distinct pathways: a reversible, two-electron, low-potential oxidation of the diarylamine and methanesulfonamide facilitated by the electron-donating 3′-OCH₃ substituent, leading to the formation of a quinone diimine; and a higher-potential, two-electron oxidation of the acridine ring, proceeding via radical cation formation followed by dimerization. Additionally, the acridine ring can undergo a one-electron reduction. The electron-donating properties and relatively low oxidation potential of the diarylamine (which is believed to be sufficiently low to permit facile oxidation in vivo) appear to be directly relevant to AMS's biological activity and its interactions with biologically significant molecules. The oxidation mechanism established at the GCE was further applied to develop a simple and efficient screening method for probing AMS interactions with biomolecules. Using an un-doped GCE setup, interactions with human serum albumin (HSA) and DNA were successfully assessed, demonstrating the potential of voltammetric techniques as effective tools in drug-biomolecule interaction studies.