Jamshidi Hoda, Naimi-Jamal Mohammad Reza, Safavi Maliheh, RayatSanati Kimia, Azerang Parisa, Tahghighi Azar
Research Laboratory of Green Organic Synthesis & Polymers, Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.
Medicinal Chemistry Laboratory, Department of Clinical Research, Pasteur Institute of Iran, Tehran, Iran.
Chem Biol Drug Des. 2022 Dec;100(6):935-946. doi: 10.1111/cbdd.14031. Epub 2022 Feb 21.
Based on the significant and diverse pharmacophore features of triazole ring and considering the potent antimicrobial properties of quinoline scaffold, 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 structure of the synthetic compounds was characterized by various spectroscopic methods. The final products of triazole/quinoline hybrids and ((prop-2-yn-1-yloxy)methyl)benzene intermediates were screened for their antibacterial (Staphylococcus aureus, Escherichia coli, Shigella flexneri, and Salmonella enterica), antifungal (Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus), and cytotoxic activities. 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. These compounds can be selected as the potential candidates for treating invasive fungal infections caused by S. cerevisiae, after further investigation. Preliminary in silico ADME studies also predicted the favorable pharmacokinetic attributes of most compounds.
基于三唑环显著且多样的药效团特征,并考虑到喹啉骨架强大的抗菌性能,通过一种成熟的合成方法(即点击化学)合成了一系列新型的含氯喹啉部分的基于1,2,3 - 三唑的多芳族化合物。通过各种光谱方法对合成化合物的结构进行了表征。对三唑/喹啉杂化物和((丙 - 2 - 炔 - 1 - 基氧基)甲基)苯中间体的最终产物进行了抗菌(金黄色葡萄球菌、大肠杆菌、弗氏志贺菌和肠炎沙门氏菌)、抗真菌(白色念珠菌、酿酒酵母和烟曲霉)及细胞毒性活性筛选。最佳抗真菌化合物对酿酒酵母的最小抑菌浓度(MIC)在0.35 - 0.63 μM范围内,且无任何细胞毒性作用。经过进一步研究后,这些化合物可被选为治疗由酿酒酵母引起的侵袭性真菌感染的潜在候选药物。初步的计算机辅助药物代谢动力学(ADME)研究也预测了大多数化合物具有良好的药代动力学特性。