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A novel approach to synthesize anti-metabolite conjugated and intense blue fluorescence emitting smart polymeric nanoparticles is reported for the efficient delivery anticancer drug and self-monitoring its effect in the drug-resistant...

Antimicrobial resistant (AMR) bacteria constitute a global health concern. Helicobacter pylori is a Gram-negative bacterium that infects about half of the human population and is a major cause of peptic ulcer disease and gastric cancer. Increasing resistance to triple and quadruple H. pylori eradication therapies poses great challenges and urges the development of novel, ideally narrow spectrum, antimicrobials targeting H. pylori. Here, we describe the antimicrobial spectrum of a family of nitrobenzoxadiazol-based antimicrobials initially discovered as inhibitors of flavodoxin: an essential H. pylori protein. Two groups of inhibitors are described. One group is formed by narrow-spectrum compounds, highly specific for H. pylori, but ineffective against enterohepatic Helicobacter species and other Gram-negative or Gram-positive bacteria. The second group includes extended-spectrum antimicrobials additionally targeting Gram-positive bacteria, the Gram-negative Campylobacter jejuni, and most Helicobacter species, but not affecting other Gram-negative pathogens. To identify the binding site of the inhibitors in the flavodoxin structure, several H. pylori-flavodoxin variants have been engineered and tested using isothermal titration calorimetry. An initial study of the inhibitors capacity to generate resistances and of their synergism with antimicrobials commonly used in H. pylori eradication therapies is described. The narrow-spectrum inhibitors, which are expected to affect the microbiota less dramatically than current antimicrobial drugs, offer an opportunity to develop new and specific H. pylori eradication combinations to deal with AMR in H. pylori. On the other hand, the extended-spectrum inhibitors constitute a new family of promising antimicrobials, with a potential use against AMR Gram-positive bacterial pathogens.

Tetrazolo[1,5‐a]quinoline‐4‐carbaldehyde, 3‐oxo‐3‐phenylpropanenitrile, and β‐enamine were reacted in one‐pot to obtain highly functionalized quinolinyl‐1,4‐dihydropyridines. In addition to spectroscopic characterization, the structure of one of the compound is confirmed by single‐crystal X‐ray diffraction. Among all compounds evaluated for cytotoxic effect against MCF7, three quinolinyl‐1,4‐dihydropyridines (SKS13, 19, and 20) were found to be most active with half inhibition concentrations value of 7.87–9.55 μM. Molecular docking of the active molecules to various breast cancer targets revealed effective compounds have multiple receptor targeting potential in breast cancer. Our results corroborate quinolinyl‐1,4‐dihydropyridines as a valuable scaffold to develop anticancer drugs.

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