Structure-based design, synthesis and biological evaluation of a NAD⁺ analogue targeting Pseudomonas aeruginosa NAD kinase.

ABSTRACT: Multidrug resistance is a major public health problem that requires the urgent development of new antibiotics and therefore the identification of novel bacterial targets. The activity of nicotinamide adenine dinucleotide kinase, NADK, is essential in all bacteria tested so far, including many human pathogens that display antibiotic resistance leading to the failure of current treatments. Inhibiting NADK is therefore a promising and innovative antibacterial strategy since there is currently no drug on the market targeting this enzyme. Through a fragment-based drug design approach, we have recently developed a NAD⁺ -competitive inhibitor of NADKs, which displayed in vivo activity against Staphylococcus aureus. Here, we show that this compound, a di-adenosine derivative, is inactiv

SUBMITTER: Rahimova R 

PROVIDER: S-EPMC10087438 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature