Department of Chemistry, Faculty of Science, Istanbul University, Fatih, 34126 Istanbul, Turkey.
Published: November 2022
AI Article Synopsis
Article Abstract
Our previous studies have revealed that the aminated 1,4-quinone scaffold can be used for the development of novel antibacterial and/or antifungal agents. In this study, the aminated quinolinequinones () were designed, synthesized, and evaluated for their antimicrobial activity against a panel of seven bacterial strains (three Gram-positive and four Gram-negative bacteria) and three fungal strains. The structure-activity relationship (SAR) for the QQs was also summarized. The antibacterial activity results indicated that the two aminated QQs ( and ) were active against (ATCC 29212) with a MIC value of 78.12 μg/mL. Besides, the two aminated QQs ( and ) were active against (ATCC 29213) with MIC values of 4.88 and 2.44 μg/mL, respectively. The most potent aminated QQs ( and ) were identified as promising lead molecules to further explore their mode of action. The selected QQs ( and ) were further evaluated to assess their potential antimicrobial activity against each of 20 clinically obtained methicillin-resistant isolates, antibiofilm activity, and bactericidal activity using time-kill curve assay. We found that the molecules prevented adhesion of over 50% of the cells in the biofilm. Molecular docking studies were performed to predict the predominant binding mode(s) of the ligands. We believe that the molecules need further investigation, especially against infections involving biofilm-forming microbes.
Our previous studies have revealed that the aminated 1,4-quinone scaffold can be used for the development of novel antibacterial and/or antifungal agents. In this study, the aminated quinolinequinones () were designed, synthesized, and evaluated for their antimicrobial activity against a panel of seven bacterial strains (three Gram-positive and four Gram-negative bacteria) and three fungal strains. The structure-activity relationship (SAR) for the QQs was also summarized.
School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington, New Zealand; Centre for Biodiscovery, Victoria University of Wellington, PO Box 600, Wellington, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand. Electronic address:
A library of thirty-two quinolinequinones (QQs) with various amine substituents at the 6- and 7-positions were synthesised efficiently and in good yields for evaluation as potential anti-tuberculosis agents. Mycobacterium tuberculosis growth inhibition assays demonstrated that QQs bearing moderate length alkyl chains (i.e.
Seventeen thousand three hundred and fifty four mildly hypertensive people with diastolic blood pressures between 90 and 109 mm Hg at screening were randomised to active treatment, with bendrofluazide or propranolol, or to placebo tablets. They were followed for a maximum of five and a half years, giving a total of 85,572 patient-years of observation. There were 456 myocardial infarctions or sudden coronary deaths.
