Exploring isoquinolinequinones as promising antibacterial agents against methicillin-resistant Staphylococcus strains: synergistic effects with clinical antibiotics and antibiofilm activity.

Finding potent alternatives to traditional antibiotics has grown ever more important as resistant pathogens continue to spread. Herein, we successfully designed and synthesised a series of isoquinolinequinones (IQQs) using a one-pot reaction strategy in acceptable yields, integrating aromatic amine moieties containing different types of groups (strongly EDG, moderately EDG, or EWG) at various positions on the phenyl ring. The synthesised IQQs were evaluated for their minimum inhibitory concentrations (MICs) using broth microdilution. The bactericidal and synergistic effects of IQQs, either alone or in combination with different traditional antibiotics, were tested using time-kill curve assays at both 1× and 4× MICs. Also, antibiofilm activities were evaluated using the microplate method. According to our results, IQQ3 and IQQ13 exhibited MIC values comparable to those of antibiotics frequently used in clinics against clinical methicillin-resistant Staphylococcus strains. Specifically, IQQ3, IQQ11, and IQQ13 exhibited synergistic effects with levofloxacin at both 1× and 4× MICs. Furthermore, IQQ3 exhibited synergistic activity with linezolid, another antibiotic frequently used in clinics, apart from levofloxacin. Moreover, these molecules showed antibiofilm activity similar to that of the tested antibiotics. Overall, our findings highlight the promise of IQQs as effective antibacterial agents, particularly in treating antibiotic-resistant infections through combination therapies, due to their low inhibitory concentrations and strong synergistic effects with existing antibiotics.