Advances in Antifungal Drug Development: An Up-To-Date Mini Review

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.

COVID-19-Associated Fungal Infections: An Urgent Need for Alternative Therapeutic Approach?

“…Novel antifungals are being currently developed to overcome these limitations especially reducing their toxicity, optimizing pharmacodynamics and pharmacokinetics, improving their formulations, and increasing specificity. Some developments have been focused on agents with new structure for a known target (rezafungin, tetrazoles, ibrexafungerp) or establish entirely novel targets (fosmanogepix, olorofim) ( Figure 1 ; Gintjee et al, 2020 ; Bouz and Doležal, 2021 ). In spite of current efforts, antifungal drug resistance remained a major concern thus introducing alternative therapeutic approaches are irrefutable.…”

“…We also highlight some aspects of new antifungal drug development with a great promise to overcome resistance issues. In particular, we focus on novel antifungal peptides as other emerging alternatives, such as agents with new structure for a known target or entirely novel targets, combination therapy of antifungals with non-antifungal drugs and quorum-sensing molecules have been recently reviewed by other authors ( Kovács and Majoros, 2020 ; Bouz and Doležal, 2021 ; Rossato et al, 2021 ).…”

Bioactive 2-pyridone-containing heterocycle syntheses using multicomponent reactions

“…66 These reasons have prompted the development of new antifungal agents with distinct action or multitargeted combination therapy. [66][67][68] In this way, N-allylquinolone derivatives 30 were obtained through a La(OTf) 3 -catalyzed threecomponent reaction and discussed in Section 2.2. Antibacterial activity (Scheme 6).…”

Synthesis, intramolecular cyclization and anti-inflammatory activity of substituted 2-(2-(Furan-2-carbonyl)hydrazono)-4-oxobutanoic Acids

“…The priority direction in pharmaceuticals and medical chemistry is the development and creation of new dosage forms with low toxicity [1][2][3][4][5][6][7]. The main cause is the chaotic usage of medicines, which leads to a loss of their efficiency.…”