Identification of Unique Quinazolone Thiazoles as Novel Structural Scaffolds for Potential Gram-Negative Bacterial Conquerors

A class of quinazolone thiazoles
was identified as new structural
scaffolds for potential antibacterial conquerors to tackle dreadful
resistance. Some prepared compounds exhibited favorable bacteriostatic
efficiencies on tested bacteria, and the most representative 5j featuring the 4-trifluoromethylphenyl group possessed superior
performances against Escherichia coli and Pseudomonas aeruginosa to norfloxacin.
Further studies revealed that 5j with inappreciable hemolysis
could hinder the formation of bacterial biofilms and trigger reactive
oxygen species generation, which could take responsibility for emerging
low resistance. Subsequent paralleled exploration discovered that 5j not only disintegrated outer and inner membranes to induce
leakage of cytoplasmic contents but also broke the metabolism by suppressing
dehydrogenase. Meanwhile, derivative 5j could intercalate
into DNA to exert powerful antibacterial properties. Moreover, compound 5j gave synergistic effects against some Gram-negative bacteria
in combination with norfloxacin. These findings indicated that this
novel structural type of quinazolone thiazoles showed therapeutic
foreground in struggling with Gram-negative bacterial infections.