چكيده به لاتين
In this research work, a novel series of 1,2,3-triazole-based polyaromatic compounds containing chloroquinoline moiety were synthesized through a well-established synthetic methodology, named click chemistry (the copper-catalyzed azide-alkyne cycloaddition [Cu-AAC] reaction). For this purpose, first, 4,7-dichloroquinoline and diverse benzyl alcohol compounds were applied to generate 4-azido-7-chloroquinoline and ((prop-2-yn-1-yloxy)methyl)benzene intermediates, respectively. Subsequently, the azide and alkyne intermediates were subjected to the CuAAC reaction in sodium ascorbate/CuSO4.5H2O in the mixed solvent of water/tert-butanol at 25°C for 24-72 h. An important advantage of this method is the ability to use cheap and green water solvent to prepare the final product from the intermediates, making this method closer to the ideal state of the principles of click chemistry. Then the crude products were refined by silica gel column chromatography and petroleum ether/dichloromethane solvents. The structure of the synthesized compounds was confirmed using HNMR, CNMR, FT-IR and GC-MS spectroscopic data. The final products of quinoline-triazole hybrids and ((prop-2-yn-1-yloxy)methyl)benzene intermediates were screened for their antibacterial (Staphylococcus aureus and Escherichia coli) and antifungal (Candida albicans and Saccharomyces cerevisiae) activities. These hybrid molecules were designed based on the significant and diverse pharmacophore properties of 1,2,3-triazole ring among nitrogen-containing heterocyclic compounds and relied on the quinoline scaffold's potent antimicrobial properties. The structure of compounds was characterized by various spectroscopic methods. The best antifungal compounds exhibited minimum inhibitory concentration (MIC), in the range of 0.35-0.63 µM, against S. cerevisiae without any cytotoxic effect. After further investigation, these compounds can be selected as potential candidates for treating invasive fungal infections caused by S. cerevisiae without any cytotoxic effect. Preliminary ADME studies have also confirmed the favourable pharmacokinetic attributes of most compounds.
