吡唑基酰胺-查耳酮缀合物：合成与抗动质体活性
Pyrazolyl amide-chalcones conjugates: Synthesis and antikinetoplastid activity.
作者信息
Agarwal Devesh S, Beteck Richard M, Mabille Dorien, Caljon Guy, Legoabe Lesetja J
机构信息
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, 2520, South Africa.
Laboratory of Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.
出版信息
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4199-4210. doi: 10.1007/s00210-024-03524-7. Epub 2024 Oct 21.
A series of novel pyrazolyl amide-chalcones conjugates was synthesized in five steps and evaluated against a range of medically important kinetoplastid parasites including Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. In addition, the series was also tested for in vitro cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all synthetised compounds, 9b was found to be the most active against T. b. brucei with an IC value of 0.51 ± 0.06 μM. Against T. b. rhodesiense, 9n was found to be the most potent with an IC value of 0.46 ± 0.07 μM. While against L. infantum, 9a was found to be most active with an IC value of 7.16 ± 1.88 μM. Based on the results and SAR, further modifications will be carried out to increase potency.
通过五步合成了一系列新型吡唑基酰胺 - 查耳酮共轭物，并针对一系列具有医学重要性的动基体寄生虫进行了评估，这些寄生虫包括克氏锥虫、布氏布氏锥虫、罗德西亚布氏锥虫和婴儿利什曼原虫。此外，还对该系列化合物针对人肺成纤维细胞和原代小鼠巨噬细胞进行了体外细胞毒性活性测试。在所有合成的化合物中，发现9b对布氏布氏锥虫的活性最高，IC值为0.51±0.06 μM。对于罗德西亚布氏锥虫，发现9n最有效，IC值为0.46±0.07 μM。而对于婴儿利什曼原虫，发现9a活性最高，IC值为7.16±1.88 μM。基于这些结果和构效关系，将进行进一步修饰以提高效力。
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