Abstract
The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets for antifungals. Novel antifungals in clinical development include first-in-class agents, new structures for an established target, and formulation modifications to marketed antifungals, in addition to repurposed agents. Membrane interacting peptides and aromatherapy are gaining increased attention in the field. Immunotherapy is another promising treatment option, with antifungal antibodies advancing into clinical trials. Novel targets for antifungal therapy are also being discovered, allowing the design of new promising agents that may overcome the resistance issue. In this mini review, we will summarize the current status of antifungal drug pipelines in clinical stages, and the most recent advancements in preclinical antifungal drug development, with special focus on their chemistry.
Highlights
Development: An Up-To-Date MiniFor decades, fungal infections have been difficult health conditions to treat
CryptococWhen comparing older antifungals withpeptidase the newer1 ones mentioned in this review, cus neoformans, as a potential target for antifungal drug development
It must be noted that in order to truly evaluate the efficacy of new antifungals in treating life-threatening infections, infection-specific biomarkers should be relied on rather than death as an endpoint, since such targeted patients have multiple health comorbidities
Summary
Fungal infections have been difficult health conditions to treat. This fact can be attributed to the narrow spectrum and high toxicity of clinically used antifungals, long duration of treatment and the high emergence of resistance towards available agents. Cryptococcus, and Aspergillus are the most common causative organisms of life-threatening human fungal infections [2]. Aspergillus fumigatus is becoming more resistant to treatment, making it more difficult to treat aspergillosis, with mortality rate reaching 100% in some cases. We will highlight current state-of-the-art developments in antifungal pipeline, both in clinical and preclinical stages, with special focus on their chemistry, in order to provide the reader with a comprehensive, up-to-date source that will influence future synthetic efforts.
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