Novel, unifying mechanism for amphotericin B and other polyenedrugs: electron affinity, radicals, electron transfer, autoxidation, toxicity, and antifungal action.

Abstract

Amphotericin B is the most important member of the macrolide polyene antibiotics. There has been recent focus on mode of action involving membrane ion channels. The present report provides extensive evidence based on literature reports and computational studies on electron affinity for a multifaceted approach to therapeutic action and drug toxicity. Aspects involved include electron affinity, electron transfer, reactive oxygen species and oxidative stress in relation to mechanisms of drug action and toxicity. Other features addressed are autoxidation, metabolism, therapeutic properties (mainly antifungal), pro-oxidant action, antioxidant properties and analogy to conjugated dicarbonyls.