The Future of Antifungal Drug Therapy: Novel Compounds and Targets

被引:105
作者
Fernandes, Caroline Mota [1 ]
Dasilva, Deveney [1 ]
Haranahalli, Krupanandan [2 ,3 ]
McCarthy, J. Brian [5 ]
Mallamo, John [5 ]
Ojima, Iwao [2 ,3 ]
Del Poeta, Maurizio [1 ,2 ,4 ,5 ,6 ]
机构
[1] SUNY Stony Brook, Dept Microbiol & Immunol, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA
[4] Vet Adm Med Ctr, Northport, NY 11768 USA
[5] MicroRid Technol Inc, Dix Hills, NY 11746 USA
[6] SUNY Stony Brook, Sch Med, Div Infect Dis, New York, NY 11794 USA
关键词
acylhydrazones; antifungal agents; arylamidine; calcineurin; drug therapy; new targets; nikkomycin; olorofilm; sphingolipids; threalose; BROAD-SPECTRUM ANTIFUNGAL; INOSITOL PHOSPHORYLCERAMIDE SYNTHASE; CELECOXIB DERIVATIVE AR-12; CANDIDA-ALBICANS; IN-VITRO; SACCHAROMYCES-CEREVISIAE; GLYOXYLATE CYCLE; SERINE PALMITOYLTRANSFERASE; 2-COMPONENT SYSTEM; STRESS RESPONSES;
D O I
10.1128/AAC.01719-20
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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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页数:13
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