Background: New antibiotics classes are desperately needed to treat drug-resistant bacterial and fungal infections. Metal complexes are ubiquitous in synthetic organic chemistry, where their versatile reactivity and 3D-geometry have found widespread application as valuable catalysts. Metals have also established themselves as a cornerstone of medicinal chemistry, with anticancer drugs such as Cisplatin constituting one of the most important chemotherapeutics in the clinics today. Several novel metal-based compounds are currently in clinical trials, highlighting their potential as an expansion of the accessible chemical space for drug-development. [1]
Materials/methods: The Community for Open Antimicrobial Drug Discovery (CO-ADD) is an open access initiative that has screened over 300,000 diverse compounds, sourced from over 250 academic groups all over the world, and tested for their antibacterial activity.[2] We have mined this unique data collection and identified nearly 1000 that are classified as metal complexes.
Results: Surprisingly, the hit-rate for metal complexes is more than ten-fold higher than that of purely organic compounds, even after accounting for cytotoxicity. While only 1000 compounds does not allow for a detailed analysis, we can identify trends for which types of metals/structures seem to be interesting. While our initial analysis focused on antibacterial activity [3], similar benefits are also seen for antifungal activity.
Conclusions: Metal complexes are promising candidates for the sourcing new antibiotics. Their diverse 3D geometry enables a higher degree of structural variety than their organic counterparts. This diversity also implies an enormous landscape of unexplored chemical space that is available through these types of compounds. Metal complex also have access to a suite of unique modes of action that differ from organic compounds. Hopefully the number of metal compounds in the CO-ADD database can be increased in the coming years, to allow for a better understanding of trends in activities and enable the development of new classes of metal-based antibiotics for clinical evaluation