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Phenyl aldehyde and propanoids exert multiple sites of action towards cell membrane and cell wall targeting ergosterol in Candida albicans

机译:在白色念珠菌中苯甲醛和丙烷类化合物对靶向麦角固醇的细胞膜和细胞壁具有多个作用位点

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摘要

In the present study, two phyto-compounds phenyl aldehyde (cinnamaldehyde) and propanoid (eugenol) were selected to explore their modes of action against . Electron microscopy, flow cytometry and spectroscopic assays were employed to determine the targets of these compounds. Treatment of (CA04) with sub-MICs of cinnamaldehyde (50 μg/mL) and eugenol (200 μg/mL) indicated multiple sites of action including damages to cell walls, cell membranes, cytoplasmic contents and other membranous structures as observed under electron microscopy. Concentration and time dependent increase in the release of cytoplasmic contents accompanied with change in extracellular K concentration was recorded. Exposure of cells at 4 × MIC of cinnaamldehyde and eugenol resulted in 40.21% and 50.90% dead cells, respectively as revealed by flow cytometry analysis. Treatment of cells by cinnamaldehyde and eugenol at 0.5 × MIC showed 67.41% and 76.23% reduction in ergosterol biosynthesis, respectively. The binding assays reflected the ability of compounds to bind with the ergosterol. Our findings have suggested that the membrane damaging effects of phenyl aldehyde and propanoids class of compounds is attributed to their ability to inhibit ergosterol biosynthesis and simultaneously binding with ergosterol. Indirect or secondary action of these compounds on cell wall is also expected as revealed by electron microscopic studies.
机译:在本研究中,选择了两种植物化合物苯醛(肉桂醛)和丙烷(丁香酚)来研究它们的抗药性。使用电子显微镜,流式细胞仪和光谱测定法确定这些化合物的靶标。用肉桂醛(50μg/ mL)和丁子香酚(200μg/ mL)的亚MIC处理(CA04)表明有多个作用位点,包括对细胞壁,细胞膜,细胞质含量和其他膜结构的破坏,如在电子显微镜下观察到的。记录了浓度和时间依赖性地增加了胞浆内容物的释放并伴随着细胞外钾浓度的变化。流式细胞仪分析显示,肉桂醛和丁子香酚在4××MIC下暴露细胞分别导致40.21%和50.90%死细胞。肉桂醛和丁子香酚在0.5×MIC下处理细胞,麦角固醇的生物合成分别减少67.41%和76.23%。结合测定反映了化合物与麦角固醇结合的能力。我们的发现表明,苯醛和类丙烷化合物的膜破坏作用归因于它们抑制麦角固醇生物合成并同时与麦角固醇结合的能力。如电子显微镜研究所揭示,还预期这些化合物对细胞壁的间接或次级作用。

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