PDF(Pubmed)
Abstract：
Organic and synthetic chemistry plays a crucial role in drug discovery fields. Moreover, chemical modifications of available molecules to enhance their efficacy, selectivity and safety have been considered as an attractive approach for the development of new bioactive agents. Indoles, a versatile group of natural heterocyclic compounds, have been widely used in pharmaceutical industry due to their broad spectrum of activities including antimicrobial, antitumoral and anti-inflammatory among others. Herein, we report the amoebicidal activity of different indole analogs on Acanthamoeba castellanii Neff. Among the 40 tested derivatives, eight molecules were able to inhibit this protistan parasite. The structure-activity relationship (SAR) analysis of their anti-Acanthamoeba activity would suggest that a carboxylation of C-3 position and the incorporation of halogen as chlorine/fluorine would enhance their biological profile, presumably by increasing their lipophilicity and therefore their ability to cross the cell membrane. Fluorescence image base system was used to investigate the effect of indole 6o c-6 on the cytoskeleton network and various programmed cell death features. We were able to highlight that the methyl 6-chloro-1H-indole-3-carboxylate could induce program cell death by the mitochondrial dysfunction.
摘要：
有机和合成化学在药物发现领域中起着至关重要的作用。此外，对可用分子进行化学修饰以增强其功效，选择性和安全性被认为是开发新的生物活性剂的有吸引力的方法。偶像崇拜,一组通用的天然杂环化合物，已被广泛用于制药工业由于其广谱的活性，包括抗菌，抗肿瘤和抗炎等。在这里，我们报告了不同吲哚类似物对castellaniiNeff的杀变形虫活性。在40个测试的衍生物中，八种分子能够抑制这种原生寄生虫。对其抗棘阿米巴活性的结构-活性关系（SAR）分析表明，C-3位置的羧化和卤素作为氯/氟的掺入将增强其生物学特性，大概是通过增加它们的亲脂性，从而增加它们穿过细胞膜的能力。荧光图像数据库系统用于研究吲哚6oc-6对细胞骨架网络和各种程序性细胞死亡特征的影响。我们能够强调6-氯-1H-吲哚-3-羧酸甲酯可以通过线粒体功能障碍诱导程序性细胞死亡。
