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<p>In the search for novel antimicrobial agents, a series of aminated quinolinequinone derivatives (AQQ1-13) were synthesized and evaluated for their in vitro antibacterial and antifungal activities. These compounds were constructed <i>via</i> sulfonamide linkers incorporating commercially available <i>p</i>-aminobenzenesulfonamides bearing diverse heteroaromatic or acyl substituents. The antibacterial activity was assessed against four gram-negative and three gram-positive bacterial strains, while antifungal activity was evaluated against three fungal species using the CLSI-approved broth microdilution method. Several compounds demonstrated moderate antimicrobial activity when compared with standard reference drugs. Notably, three AQQs (AQQ7, AQQ9, and AQQ11) exhibited notable antibacterial activity against <i>Enterococcus faecalis</i>, with a minimum inhibitory concentration (MIC) value of 78.12&#xa0;µg/mL, showing lower MIC values than amikacin under the tested conditions (MIC = 128&#xa0;µg/mL) under the same conditions. Time-kill studies revealed bactericidal effects at 1× and 4× MIC levels, while combination studies demonstrated synergistic interactions with levofloxacin, particularly for AQQ11. Furthermore, AQQ9 and AQQ11 exhibited antibiofilm activity in combination therapy, including inhibition of biofilm formation and partial disruption of preformed biofilms. In silico ADMET and molecular docking analyses identified AQQ9 as a compound of interest, showing favorable drug-likeness properties and favourable binding interactions toward <i>E. faecalis</i> DNA gyrase. Overall, these findings highlight quinolinequinone-based sulfonamide bioisosteres as potential scaffolds for further development of combination therapies targeting gram-positive and biofilm-associated infections.</p>

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Quinolinequinone-based sulfonamide bioisosteres as promising antimicrobial agents

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月28日

查看全文
  • Hatice Yıldırım,
  • Mahmut Yıldız,
  • Nilüfer Bayrak,
  • Bekir Özer,
  • Duraisamy Sridhar,
  • Emel Mataracı-Kara,
  • Subramaniam AnandaThangadurai,
  • Venkatesan Jayaprakash,
  • Amaç Fatih TuYuN

摘要

In the search for novel antimicrobial agents, a series of aminated quinolinequinone derivatives (AQQ1-13) were synthesized and evaluated for their in vitro antibacterial and antifungal activities. These compounds were constructed via sulfonamide linkers incorporating commercially available p-aminobenzenesulfonamides bearing diverse heteroaromatic or acyl substituents. The antibacterial activity was assessed against four gram-negative and three gram-positive bacterial strains, while antifungal activity was evaluated against three fungal species using the CLSI-approved broth microdilution method. Several compounds demonstrated moderate antimicrobial activity when compared with standard reference drugs. Notably, three AQQs (AQQ7, AQQ9, and AQQ11) exhibited notable antibacterial activity against Enterococcus faecalis, with a minimum inhibitory concentration (MIC) value of 78.12 µg/mL, showing lower MIC values than amikacin under the tested conditions (MIC = 128 µg/mL) under the same conditions. Time-kill studies revealed bactericidal effects at 1× and 4× MIC levels, while combination studies demonstrated synergistic interactions with levofloxacin, particularly for AQQ11. Furthermore, AQQ9 and AQQ11 exhibited antibiofilm activity in combination therapy, including inhibition of biofilm formation and partial disruption of preformed biofilms. In silico ADMET and molecular docking analyses identified AQQ9 as a compound of interest, showing favorable drug-likeness properties and favourable binding interactions toward E. faecalis DNA gyrase. Overall, these findings highlight quinolinequinone-based sulfonamide bioisosteres as potential scaffolds for further development of combination therapies targeting gram-positive and biofilm-associated infections.