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

Abstract

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.

Derivatization of Marine‐Derived Fascaplysin via Highly Regioselective Suzuki‐Miyaura Coupling Contributing to the Enhanced Antibacterial Activity

“…Reaction conditions: all compounds were synthesized under nitrogen protection. [28] which were eight-time more active than fascaplysin and comparable to the antibiotic colistin. Further studies are underway with more fascaplysin derivatives.…”

Natural Berberine-Hybridized Benzimidazoles as Novel Unique Bactericides against Staphylococcus aureus

“…The successful applications of antibacterial azoles greatly hindered the invasion of bacteria in humans, terrestrial and aquatic animals, as well as plants. − In particular, benzimidazoles have attracted considerable attention because of the purine-like structure in benzimidazole ring that enabled benzimidazole derivatives to block the biosynthesis of proteins and nucleic acids. , A variety of bactericides containing benzimidazole fragment have been launched into the market, such as carbendazim and thiabendazole, demonstrating the enormous potentiality in the antibacterial aspect.…”

Design and Synthesis of Sulfanilamide Aminophosphonates as Novel Antibacterial Agents towards Escherichia coli

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