| Popis: |
The development of new antimicrobial agents is necessary to overcome the emerging antimicrobial resistance among infectious microbial pathogens. Herein, we successfully designed and synthesized quinolinequinones (QQs) with N-phenylpiperazine (QQ1-7) containing strong or weak EDG in the amino moiety by converting hydroxyquinoline (HQ) to the dichloroquinolinequinone (QQ) via chlorooxidation. We performed an extensive antimicrobial activity assessment of the QQs with N-phenylpiperazine (QQ1-7). Among the seven quinolinequinones (QQs) with N-phenylpiperazine tested, QQ3 and QQ4 were the most active molecules against Staphylococcus aureus (ATCC® 29213) with a MIC value of 1.22 μg/mL. In addition to this, while QQ4 was more than six (6) times more effective towards Enterococcus faecalis (ATCC® 29212), QQ3 was twenty-six (26) times more effective against same strain. Furthermore, the evaluation of antimicrobial activity indicated that six of seven synthesized QQs (QQ1-4, QQ6, and QQ7) exhibited superior biological potency, eight (8) times for five of them (QQ1-4 and QQ6) and two (2) times for QQ7, against Staphylococcus epidermidis (ATCC® 12228). Besides, all QQs except QQ5 displayed excellent antifungal activity against the fungi Candida albicans (ATCC® 10231). Among these, the two QQs (QQ3 and QQ4), which showed the lowest values against gram-positive bacterial strains (Staphylococcus aureus (ATCC® 29213), Staphylococcus epidermidis (ATCC® 12228), and Enterococcus faecalis (ATCC® 29212)) as well as fungal strains (Candida albicans (ATCC® 10231) and Candida parapsilosis (ATCC® 22019)), were further evaluated for their biofilm inhibition properties and their mode of action with in vitro potential antimicrobial activity against each of 20 clinically obtained resistant strains of gram-positive bacteria, and bactericidal activity using time-kill curve assay. In this study, we investigated the bactericidal effects of QQ3 against methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans strains. The findings of this study suggest that a significant bactericidal effect was seen with all tested 1 × MIC and 4 × MIC concentrations used within 24 h. Our findings present significant implications for an antimicrobial drug candidate for treating infections, especially those caused by clinically resistant MRSA isolates. |
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