Deciphering the antimicrobial activity of phenanthroline chelators

Abstract

The opportunistic fungal pathogen, Candida albicans, causes a range of diseases in susceptible individuals. The adverse side effects of many of the current anti-fungal prescription drugs and the emergence of C. albicans isolates and other Candida species which are resistant to these compounds have accelerated the search for new drug candidates which have different modes of action. A family of metal chelators, which are based on the 1,10-phenanthroline core, exhibit excellent growth inhibitory effects in vitro against a number of Candida species, including clinical isolates. The compounds sequester transition metal ions, damage mitochondrial function and uncouple cell respiration. Additionally, fungal cell morphology undergoes dramatic changes and there is evidence of apoptotic cell death. Importantly, in vivo studies have confirmed that the compounds have an acceptably low toxicity profile.