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Apolipoprotein B mRNA‐editing enzyme catalytic polypeptide like (APOBEC) DNA cytidine deaminases convert cytosine to uracil in pathogen‐related single‐stranded DNAs. Aberrant activation of APOBEC enzymes in tumour cells leads to hypermutations that drive heterogeneity and clonal evolution, which results in tumour progression and treatment adaptation. APOBEC3 family member APOBEC3B (A3B) is a promising drug target to combat drug resistance, but the discovery of potent lead compounds remained challenging. Here, we devised a BspH1 restriction enzyme‐based biosensor to measure APOBEC deaminase activity, with superior simplicity and without the need of counter assays. Using this method, we performed a proof‐of‐concept screening using series of flavonoids and dihydrochalcones, from which bona fide inhibitors of recombinant A3B were identified and further validated by isothermal titration calorimetry. Our results demonstrate the capability of the BspH1‐based biosensor as a method for HTS, and prospects of developing potent A3B inhibitors using flavonoid and dihydrochalcone backbones.

Aims The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. Methods and Results The results showed that compound 1 suppressed the expression of QS‐related genes and showed the best inhibitory activity to the pqs system of wild‐type Ps. aeruginosa PAO1 with an IC50 of 20.22 μmol L−1. The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration‐dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand‐binding domain of the Lys‐R type transcriptional regulator PqsR as a competitive antagonist. Conclusions The quinoline‐based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. Significance and Impact of Study The study showed that the quinoline‐based derivatives could be used as an anti‐virulence agent for treating Ps. aeruginosa infections.