4.7 Review

The Future of Antifungal Drug Therapy: Novel Compounds and Targets

Journal

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 2, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01719-20

Keywords

acylhydrazones; antifungal agents; arylamidine; calcineurin; drug therapy; new targets; nikkomycin; olorofilm; sphingolipids; threalose

Funding

  1. NIH [AI136934, AI116420, AI125770, I01BX002924]
  2. Veterans Affairs Program

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Fungal infections are a significant problem in immunocompromised patients, and existing antifungal agents have limitations that prompt the need for novel drugs. Recent years have seen advances in antifungal drug development with new compounds in various stages of development.
Fungal infections are a universal problem and are routinely associated with high morbidity and mortality rates in immunocompromised patients. Existing therapies comprise five different classes of antifungal agents, four of which target the synthesis of ergosterol and cell wall glucans. However, the currently available antifungals have many limitations, including poor oral bioavailability, narrow therapeutic indices, and emerging drug resistance resulting from their use, thus making it essential to investigate the development of novel drugs which can overcome these limitations and add to the antifungal armamentarium. Advances have been made in antifungal drug discovery research and development over the past few years as evidenced by the presence of several new compounds currently in various stages of development. In the following minireview, we provide a comprehensive summary of compounds aimed at one or more novel molecular targets. We also briefly describe potential pathways relevant for fungal pathogenesis that can be considered for drug development in the near future.

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