There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 μM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

Detector dogs could be trained to find invasive insect pests at borders before they establish in new areas. However, without access to the live insects themselves, odor training aids are needed to condition dogs to their scent. This proof-of-concept study assessed 2 potential training aids for insect detection: a scent extract and dead specimens of the target species. Using Musgraveia sulciventris (Hemiptera: Tessaratomidae) as an experimental model, gas chromatography-mass spectrometry (GC-MS) analyses were carried out to compare the chemical headspaces that make up the odors of live specimens and these 2 training aids. This was then followed by canine scent-detection testing to investigate biosecurity detector dogs' (n = 4) responses to training in an ecologically valid context. Both the scent extract and the dead specimens shared the majority of their volatile organic compounds (VOCs) with live insects. Of the dogs trained with scent extract (n = 2), both were able to detect the live insects accurately, and of those trained with dead specimens (n = 2), one detected the live insects accurately. These findings lend support for these training aids as odor-proxies for live insects-particularly scent extract, which is a relatively novel product with the potential for broad application to facilitate and improve insect-detection training.