Journal
CHEMBIOCHEM
Volume 24, Issue 19, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202300247
Keywords
AMR; antifungal drugs; inorganic medicinal chemistry; metalloantibiotics; metals in medicine
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Infections associated with antibiotic resistance (AMR) are projected to become the leading cause of death in the coming decades due to over-prescription of antibiotics and a lack of new drug development. A community-driven initiative, Community for Open Antimicrobial Drug Discovery (CO-ADD), has identified metal-based drugs as a potential and untapped source for combating AMR. Testing of 18 palladium (Pd) and ruthenium (Ru) complexes has revealed that Pd complexes, particularly Pd1, exhibit potent antifungal activity against Candida glabrata. Furthermore, in-vivo studies in Galleria mellonella larvae have demonstrated the non-toxic nature of these compounds.
Infections associated with antimicrobial resistance (AMR) are poised to become the leading cause of death in the next few decades, a scenario that can be ascribed to two phenomena: antibiotic over-prescription and a lack of antibiotic drug development. The crowd-sourced initiative Community for Open Antimicrobial Drug Discovery (CO-ADD) has been testing research compounds contributed by researchers around the world to find new antimicrobials to combat AMR, and during this campaign has found that metallodrugs might be a promising, yet untapped source. To this end, we submitted 18 Pd-II- and Ru-II-pyridyl-1,2,3-triazolyl complexes that were developed as catalysts to assess their antimicrobial properties. It was found that the Pd complexes, especially Pd1, possessed potent antifungal activity with MICs between 0.06 and 0.125 mu gmL(-1) against Candida glabrata. The in-vitro studies were extended to in-vivo studies in Galleria mellonella larvae, where it was established that the compounds were nontoxic. Here, we effectively demonstrate the potential of Pd-II-pyta complexes as antifungal agents.
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