New approaches to the treatment of giardiasis

Abstract

Giardiasis is one of the most common causes of diarrheal disease worldwide, yet existing antimicrobial therapies are not always effective and drug resistance occurs in vivo and in vitro. The review focuses on recent advances in the development of new antigiardial drug candidates. Modification of existing drug leads is a major strategy to develop new high-potency drugs. Complex derivatives of 5-nitroimidazole, the core structure of the most commonly used antigiardial drug, metronidazole, have shown significantly improved activities against Giardia and the ability to overcome metronidazole resistance. Derivatives of benzimidazole, the structural core of the effective antigiardial albendazole, are also exhibiting promising new activities. Beyond lead modifications, several new classes of antigiardial drug candidates have recently been identified by high-throughput screening of large compound libraries, and first efforts have been reported on the development of drugs tailored to known molecular targets in Giardia. The pipeline of new antigiardial drug candidates has significantly expanded over the last few years, but this expansion has so far not been accompanied by demonstration of efficacy in animal models or by a clear understanding of the action mechanisms, particularly in regard to new nitro antimicrobials. Many challenges are still to be expected before clinical utility of new antigiardial drugs can be established.