Activity of Fluorine-Containing Analogues of WC-9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii.
Activity of Fluorine-Containing Analogues of WC-9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii.
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WC-9 的含氟类似物和结构相关类似物对抗两种细胞内寄生虫：克氏锥虫和弓形虫的活性。
DOI：
10.1002/cmdc.201600505
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发表时间：
2016
期刊：
影响因子：
3.4
通讯作者：
Rodriguez,JuanB
中科院分区：
文献类型：
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作者：
Chao,MaríaN;Li,Catherine;Storey,Melissa;Falcone,BrunoN;Szajnman,SergioH;Bonesi,SergioM;Docampo,Roberto;Moreno,SilviaNJ;Rodriguez,JuanB
Two obligate intracellular parasites,Trypanosoma cruzi, the agent of Chagas disease, andToxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related toWC‐9(4‐phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect onT. cruziandT. gondiigrowth in tissue culture cells. Two fluorine‐containing derivatives, the 3‐(3‐fluorophenoxy)‐ and 3‐(4‐fluorophenoxy)phenoxyethyl thiocyanates, exhibited half‐maximal effective concentration (EC50) values of 1.6 and 4.9 μm, respectively, against tachyzoites ofT. gondii, whereas they showed similar potency toWC‐9against intracellularT. cruzi(EC50values of 5.4 and 5.7 μm, respectively). In addition, 2‐[3‐ (phenoxy)phenoxyethylthio]ethyl‐1,1‐bisphosphonate, which is a hybrid inhibitor containing 3‐phenoxyphenoxy and bisphosphonate groups, has activity againstT. gondiiproliferation at sub‐micromolar levels (EC50=0.7 μm), which suggests a combined inhibitory effect of the two functional groups.
