Mechanisms of Action of DNA Intercalating Acridine-based Drugs: How Important are Contributions from Electron Transfer and Oxidative Stress?

Title: Mechanisms of Action of DNA Intercalating Acridine-based Drugs: How Important are Contributions from Electron Transfer and Oxidative Stress?

Volume: 10 Issue: 24

Author(s): Bruce C. Baguley, Laurence P.G. Wakelin, Jason D. Jacintho and Peter Kovacic

Affiliation:

Keywords: dna intercalation, anticancer, amsacrine, daca, electron transfer, charge transfer

Abstract: Reactive oxygen species (ROS) are produced continuously in living cells as a by-product of respiration and other metabolic activity. Some ROS may react with DNA, and in some cases may abstract an electron from the double helix, leading to long range electron transfer (ET) reactions. Thus, the DNA of living cells may be in a continuous state of ET. We consider here whether acridine-based anticancer or antimicrobial drugs, which bind to DNA by intercalation, might either donate electrons to, or accept electrons from, the double helix, thus actively participating in ET reactions. We focus in particular on two acridine-based drugs that have been tested against human cancer in the clinic. Amsacrine is a 9-anilinoacridine derivative that appears to act as an electron donor in ET reactions on DNA, while N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) may act as an electron acceptor. Such reactions may make important contributions to the antitumor activity of these drugs.

Cite this article as:

Baguley C. Bruce, Wakelin P.G. Laurence, Jacintho D. Jason and Kovacic Peter, Mechanisms of Action of DNA Intercalating Acridine-based Drugs: How Important are Contributions from Electron Transfer and Oxidative Stress?, Current Medicinal Chemistry 2003; 10 (24) . https://dx.doi.org/10.2174/0929867033456332