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Sterol 14-Demethylase Inhibitors for Trypanosoma cruzi Infections

  • Chapter
Drug Targets in Kinetoplastid Parasites

Part of the book series: Advances In Experimental Medicine And Biology ((AEMB,volume 625))

Abstract

Chagas disease is caused by infection with the protozoan pathogen, Trypanosoma cruzi. The only approved therapeutics for treating Chagas disease are two nitroheterocydic compounds (benznidazole and nifurtimox) that are suboptimal due to poor curative activity for chronic Chagas disease and high rates of adverse drug reactions. Sterol 14-demethylase inhibitors include azole antifungal drugs such as ketoconazole, fluconazole, itraconazole, and others. The first reports of potent activity of azole antifungal drugs against Trypanosoma cruzi came out about 25 years ago. Since then, a sizeable literature has accumulated on this topic. Newer triazole compounds such as posaconazole and D0870 have been shown to be effective at curing mice with chronic Trypanosoma cruzi infection. Small clinical studies with ketoconazole or itraconazole in humans with chronic Chagas disease have not demonstrated significant curative activity. However, there is good reason for optimism that newer compounds with greater potency and improved pharmacokinetic properties might be more efficacious. Data have been published demonstrating synergistic activity of azole drugs with various other compounds, indicating that combination chemotherapy may be an effective strategy as this field moves ahead. In light of the near absence of adequate therapeutics for curing patients with chronic Chagas disease, additional effort to develop better drugs needs to be a priority.

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Authors and Affiliations

  1. Department of Medicine, University of Washington, Seattle, Washington, USA

    Frederick S. Buckner

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  1. Frederick S. Buckner
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  1. Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, Kolkata, India

    Hemanta K. Majumder

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Buckner, F.S. (2008). Sterol 14-Demethylase Inhibitors for Trypanosoma cruzi Infections. In: Majumder, H.K. (eds) Drug Targets in Kinetoplastid Parasites. Advances In Experimental Medicine And Biology, vol 625. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77570-8_6

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