Drug repurposing strategies in the development of potential antifungal agents

Abstract

The morbidity and mortality caused by invasive fungal infections are increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is a potential way of expanding the application of existing drugs. Recently, various existing drugs have been shown to be useful in the prevention and treatment of invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up-to-date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field. Key points • Conventional antifungal agents have limitations due to the occurrence of drug-resistant strains. • Non-antifungal drugs act as antifungal agents in various ways toward different targets. • Non-antifungal drugs with antifungal activity are demonstrated as effective antifungal strategies.

Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria

“…Therefore, the repeated or widespread use of AZT as a repurposed drug against Gram-negative bacteria, especially E. coli , and associated therapies will expand difficult-to-treat bacterial populations. Since CPX usage is similar to that of AZT for its anticancer, antiviral, and antibacterial activities [ 2 , 57 , 58 , 59 ], it is necessary to test whether CPX eliminates AZT-resistant bacteria. For this purpose, tdk -knockout E. coli (Keio- tdk ) [ 44 ], which lacks thymidine kinase (Tdk) expression, was used as a model of AZT-resistant strain.…”

“…Many non-antibiotic drugs used as anticancer, antifungal, anthelmintic, and anti-inflammatory agents possess antibacterial properties [ 2 , 3 , 4 ], and ~20 such drugs have been identified as candidates for drug repurposing or as adjuvants to antibiotics against MDR Gram-negative bacteria, including Escherichia coli ( E. coli ) [ 5 , 6 ].…”

Antifungal Activity of Sodium New Houttuyfonate Against Aspergillus fumigatus in vitro and in vivo

“…Unfortunately, the current antifungal agents are unsatisfactory. Drug repurposing is a promising technique to develop antifungal treatments, which has identified several non-antifungal agents with antifungal activity, such as antibacterial drugs, immunosuppressants, and statins ( Kim et al, 2020 ; Zhang et al, 2021 ). SNH, initially used the treatment of respiratory infections, was also found to have anti-fungal activity against C. albicans ( Shao et al, 2017 ; Wu et al, 2020 ).…”

“…Therefore, new antifungal agents are urgently needed, particularly for triazole-resistant strains. Although many investigations are being conducted to develop new and effective compounds, the bioactive molecules derived from existing drugs may be promising treatments ( Zhang et al, 2021 ).…”

Therapeutic Effect of an Antibody-Derived Peptide in a Galleria mellonella Model of Systemic Candidiasis

“…The mortality rate of deep-seated mycoses remains unacceptably high, especially in immunocompromised patients, partially due to the insufficient antifungal armamentarium and the increasingly reported fungal resistance [4,5]. New antifungal therapies are under investigation, including new compounds directed to novel molecular targets, new formulations, associations between conventional antifungal drugs and other agents, and drug repurposing of existing drugs [6][7][8][9][10]. Nevertheless, only a few compounds are currently undergoing clinical trials for invasive fungal infections [11][12][13].…”