Instituto Nacional de Pesquisa da Amazônia-INPA, Av. André Araújo 2936, 69067-375 Manaus, AM, Brazil.
Molecules. 2013 Aug 2;18(8):9219-40. doi: 10.3390/molecules18089219.
Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria.
疟原虫和间日疟原虫寄生虫现在对大多数用于治疗的药物都具有耐药性，或者表现出耐药的迹象。需要具有新的抗疟作用机制的新型化学实体。新型抗疟药可阻断疟原虫属从人类传播到疟蚊媒介，这是消除疟疾工作的关键。尽管间日疟原虫引起了相当数量的疟疾病例，但长期以来一直被忽视。间日疟可能导致严重的表现和死亡；因此，需要对间日疟原虫进行研究。传统医学中使用的植物，即青蒿和金鸡纳树，分别是青蒿素和奎宁这两种抗疟天然产物的来源。基于这些化合物，已经开发出了半合成青蒿素衍生物和合成喹啉类抗疟药，是目前治疗疟疾的武器库中最重要的药物。在以间日疟原虫为主的亚马逊地区，当地有使用植物衍生制剂治疗疟疾的传统。在这里，我们回顾了目前的恶性疟原虫和间日疟原虫药物敏感性检测方法，重点介绍了针对间日疟原虫的药物发现的挑战和前景，包括对休眠子的检测。我们还介绍了我们小组和其他小组在亚马逊植物的抗疟和抗疟化学成分方面的最新发现，这些发现可能是针对疟疾的潜在药物先导物。
