Insuasty Daniel, Vidal Oscar, Bernal Anthony, Marquez Edgar, Guzman Juan, Insuasty Braulio, Quiroga Jairo, Svetaz Laura, Zacchino Susana, Puerto Gloria, Abonia Rodrigo
Departamento de Química y Biología, Universidad del Norte, Km 5 vía Puerto Colombia, Barranquilla 081007, Colombia.
Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
Antibiotics (Basel). 2019 Nov 28;8(4):239. doi: 10.3390/antibiotics8040239.
Eight quinoline-based hydroxyimidazolium hybrids were prepared and evaluated in vitro against a panel of clinically important fungal and bacterial pathogens, including mycobacteria. Hybrid compounds showed remarkable antifungal activity against with a minimum inhibitory concentration (MIC) value of 15.6 µg/mL. Against other opportunistic fungi such as spp. and 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 displayed >50% inhibition against 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 also demonstrated inhibition of at 20 µg/mL (47 µM). Hybrids and were the most potent against H37Rv with MIC values of 20 and 10 µg/mL (46 and 24 µM), respectively. The hybrid demonstrated high selectivity in killing and 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.
制备了八种喹啉基羟基咪唑鎓杂化物，并对包括分枝杆菌在内的一系列具有临床重要性的真菌和细菌病原体进行了体外评估。杂化化合物对其显示出显著的抗真菌活性，最低抑菌浓度（MIC）值为15.6 µg/mL。针对其他机会性真菌，如 spp. 和 spp.，这些杂化物的MIC值为62.5 µg/mL。关于它们的抗菌活性，所有合成杂化物对革兰氏阴性菌的抑制作用很小（MIC≥50 µg/mL），然而，杂化物在20 µg/mL时对显示出>50%的抑制作用，在50 µg/mL时完全抑制。此外，该杂化物被证明是一种有效的抗葡萄球菌分子，MIC值为2 µg/mL（5 µM）。此外，杂化物在20 µg/mL（47 µM）时也显示出对的抑制作用。杂化物和对H37Rv的活性最强，MIC值分别为20和10 µg/mL（46和24 µM）。与哺乳动物细胞相比，杂化物在杀死和H37Rv方面表现出高选择性（SI>20），因此它可被视为用于作用机制研究和相关化学空间探索的先导分子。
