Antimicrobial Activity of Quinoline-Based Hydroxyimidazolium Hybrids

Abstract

Eight quinoline-based hydroxyimidazolium hybrids <b>7a-h</b> were prepared and evaluated in vitro against a panel of clinically important fungal and bacterial pathogens, including mycobacteria. Hybrid compounds <b>7c-d</b> showed remarkable antifungal activity against <i>Cryptococcus neoformans</i> with a minimum inhibitory concentration (MIC) value of 15.6 µg/mL. Against other opportunistic fungi such as <i>Candida</i> spp. and <i>Aspergillus</i> spp., these hybrids showed MIC values of 62.5 µg/mL. Regarding their antibacterial activity, all the synthetic hybrids demonstrated little inhibition of Gram-negative bacteria (MIC ≥50 µg/mL), however, hybrid <b>7b</b> displayed >50% inhibition against <i>Klebsiella pneumoniae</i> at 20 µg/mL and full inhibition at 50 µg/mL. Moreover, this hybrid was shown to be a potent anti-staphylococcal molecule, with a MIC value of 2 µg/mL (5 µM). In addition, hybrid <b>7h</b> also demonstrated inhibition of <i>Staphylococcus aureus</i> at 20 µg/mL (47 µM). Hybrids <b>7a</b> and <b>7b</b> were the most potent against <i>Mycobacterium tuberculosis</i> H37Rv with MIC values of 20 and 10 µg/mL (46 and 24 µM), respectively. The <b>7b</b> hybrid demonstrated high selectivity in killing <i>S. aureus</i> and <i>M. tuberculosis</i> H37Rv in comparison with mammalian cells (SI >20), and thus it can be considered a hit molecule for mechanism of action studies and the exploration of related chemical space.