Centro de Pesquisas Rene Rachou, Laboratório de Malária, Belo Horizonte, Brazil.
Pontifical Catholic University of Rio de Janeiro, Department of Chemistry, Rio de Janeiro, Brazil.
Int J Parasitol Drugs Drug Resist. 2018 Dec;8(3):459-464. doi: 10.1016/j.ijpddr.2018.10.002. Epub 2018 Oct 13.
In spite of recent efforts to eradicate malaria in the world, this parasitic disease is still considered a major public health problem, with a total of 216 million cases of malaria and 445,000 deaths in 2016. Artemisinin-based combination therapies remain effective in most parts of the world, but recent cases of resistance in Southeast Asia have urged for novel approaches to treat malaria caused by Plasmodium falciparum. In this work, we present chloroquine analogs that exhibited high activity against sensitive and chloroquine-resistant P. falciparum blood parasites and were also active against P. berghei infected mice. Among the compounds tested, DAQ, a chloroquine analog with a more linear side chain, was shown to be the most active in vitro and in vivo, with low cytotoxicity, and therefore may serve as the basis for the development of more effective chloroquine analogs to aid malaria eradication.
尽管世界上最近一直在努力消灭疟疾，但这种寄生虫病仍然被认为是一个主要的公共卫生问题，2016 年全球共有 2.16 亿例疟疾和 44.5 万人死亡。以青蒿素为基础的联合疗法在世界大部分地区仍然有效，但最近在东南亚出现的抗药性病例促使人们寻求新的方法来治疗由恶性疟原虫引起的疟疾。在这项工作中，我们提出了氯喹类似物，它们对敏感和氯喹耐药的恶性疟原虫血液寄生虫表现出高活性，并且对感染伯氏疟原虫的小鼠也具有活性。在所测试的化合物中，具有更线性侧链的氯喹类似物 DAQ 表现出最活跃的体外和体内活性，细胞毒性低，因此可能成为开发更有效的氯喹类似物以帮助消除疟疾的基础。
