Electrochemistry of chemotherapeutic alkylating agents and their interaction with DNA

Alkylating agents were among the first anticancer drugs to be discovered and continue to be the most commonly used in chemotherapy. They are electrophiles that react with the ring nitrogen and extracyclic oxygen atoms of DNA bases, forming covalent adducts that further lead to cross-linking of DNA strands, abnormal base pairing or DNA strand breaks. The investigation and quantitative analysis of alkylating agents in biological samples are essential for monitoring the therapy progression and efficiency, understanding their pharmacokinetics and develop new more effective and specific chemotherapeutical drugs. Among biotechnological methods, electrochemical techniques are particularly important in pharmaceutical medicine, owing to their rapid detection, great sensitivity, robustness, exceptional detection limits, ability to be used with small analyte volumes in turbid biofluids, and easy adaptability to miniaturization and point-of-care (POC) testing. This article provides first an exhaustive review concerning the electrochemical methods of characterization and quantification of different classes of chemotherapeutic alkylating agents (triazenes and hydrazines, nitrosoureas, nitrogen mustards, oxazaphosphorines, alkyl alkane sulfonates and ethylene imines) in standard samples, pharmaceutical formulations and biological matrixes. The second part of the article focuses on the recent electrochemical methodologies and DNA-electrochemical biosensors developed to study the interaction of alkylating agents with DNA. These studies are relevant for obtaining real-time details about the alkylating agents' mechanism of action and for assessing the oxidative DNA damage they cause, important for the development of improved antineoplastic drugs.