Effect on ribonucleotide reductase of novel lipophilic iron chelators: the desferri-exochelins

Desferri-exochelins are siderophores secreted by Mycobacterium tuberculosis that are both lipid- and water-soluble and have a high binding affinity for iron. Desferri-exochelin 772SM inhibits DNA replication and ribonucleotide reductase activity at 10-fold less concentration than the lipid-insoluble iron chelator deferoxamine, which is currently in clinical use. Neither chelator can extract iron directly from ribonucleotide reductase. However, because of its lipid-solubility and high binding affinity, desferri-exochelin is able to enter cells rapidly and access intracellular iron, while deferoxamine has limited capacity to cross the cell membrane.