Targeting Pathogenic Formate-Dependent Bacteria with a Bioinspired Metallo-Nitroreductase Complex.
Cheng WengHui YangBoon Shing LohMing Wah WongWee Han AngPublished in: Journal of the American Chemical Society (2023)
Nitroreductases (NTRs) constitute an important class of oxidoreductase enzymes that have evolved to metabolize nitro-containing compounds. Their unique characteristics have spurred an array of potential uses in medicinal chemistry, chemical biology, and bioengineering toward harnessing nitro caging groups and constructing NTR variants for niche applications. Inspired by how they carry out enzymatic reduction via a cascade of hydride transfer reactions, we sought to develop a synthetic small-molecule NTR system based on transfer hydrogenation mediated by transition metal complexes harnessing native cofactors. We report the first water-stable Ru-arene complex capable of selectively and fully reducing nitroaromatics into anilines in a biocompatible buffered aqueous environment using formate as the hydride source. We further demonstrated its application to activate nitro-caged sulfanilamide prodrug in formate-abundant bacteria, specifically pathogenic methicillin-resistant Staphylococcus aureus . This proof of concept paves the way for a new targeted antibacterial chemotherapeutic approach leveraging on redox-active metal complexes for prodrug activation via bioinspired nitroreduction.
Keyphrases
- cancer therapy
- methicillin resistant staphylococcus aureus
- small molecule
- transition metal
- drug release
- drug delivery
- staphylococcus aureus
- big data
- ionic liquid
- electron transfer
- copy number
- hydrogen peroxide
- protein protein
- high throughput
- gram negative
- artificial intelligence
- nitric oxide
- machine learning
- human health
- gene expression
- risk assessment
- water soluble
- mass spectrometry
- multidrug resistant
- climate change
- essential oil
- quantum dots