Small molecules with structural similarities to siderophores as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis

Drugs inhibiting the iron scarcity-induced, siderophore-mediated iron-scavenging systems of Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) may provide new therapeutic lines of defense. Compounds with structural similarities to siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions, which mimic the iron scarcity these pathogens encounter and must adapt to in the host, and under standard iron-rich conditions for comparison. New antimicrobials were identified, some of which warrant exploration as initial leads against potentially novel targets and small-molecule tools to assist in the elucidation of targets specific to iron-scarcity adapted Mtb and Yp. (C) 2008 Elsevier Ltd. All rights reserved.