Moncada-Basualto Mauricio, Lapier Michel, Maya Juan Diego, Matsuhiro Betty, Olea-Azar Claudio, Delogu Giovanna L, Uriarte Eugenio, Santana Lourdes, Matos Maria Joao
Laboratory of Free Radicals and Antioxidants, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile.
Laboratory of Carbohydrates, Faculty of Chemistry and Biology, University of Santiago of Chile, Libertador Bernardo O´Higgins 3363, Estacion Central, Santiago, Chile.
Med Chem. 2018;14(6):573-584. doi: 10.2174/1573406414666180419113437.
Neglected diseases are becoming more prevalent due to globalization. This has inspired active research in the development of new drugs for the treatment of parasitic diseases such as Chagas disease.
With the aim of finding new trypanocidal agents, we report the in vitro evaluation of a new series of 3-amidocoumarins with or without hydroxyl substituents at position 4 of the coumarin ring.
Electrochemical and biological assays were performed in order to assess the antioxidant and trypanocidal potential of these compounds and to better understand the mechanisms involved in their activity.
Most of the studied compounds showed high trypanocidal activity against both epimastigote and trypomastigote forms, with IC50 values in the low micromolar range. Some of them have greater activity and selectivity than the reference compound, nifurtimox.
Compound 2 is the most active of this series, being also non-cytotoxic against murine RAW 264.7 macrophages. Electrochemical and radical scavenging experiments were carried out, providing new information about the profile of the best derivatives, and the potential therapeutic application of the new 3-amidocoumarins.
由于全球化，被忽视的疾病正变得越来越普遍。这激发了对开发治疗诸如恰加斯病等寄生虫病新药的积极研究。
为了寻找新的杀锥虫剂，我们报告了一系列新的3-氨基香豆素在香豆素环4位有无羟基取代基的体外评价。
进行了电化学和生物学测定，以评估这些化合物的抗氧化和杀锥虫潜力，并更好地理解其活性所涉及的机制。
大多数研究化合物对前鞭毛体和锥鞭毛体形式均显示出高杀锥虫活性，IC50值在低微摩尔范围内。其中一些化合物比参比化合物硝呋莫司具有更高的活性和选择性。
化合物2是该系列中活性最高的，对小鼠RAW 264.7巨噬细胞也无细胞毒性。进行了电化学和自由基清除实验，提供了有关最佳衍生物概况以及新的3-氨基香豆素潜在治疗应用的新信息。
