Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes
Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes
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DOI：
10.1128/aac.00967-06
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发表时间：
2007-04-01
影响因子：
4.9
通讯作者：
Meunier, Bernard
中科院分区：
文献类型：
--
作者：
Benoit-Vical, Francoise;Lelievre, Joel;Meunier, Bernard
疟疾是世界上第三大传染病病因。由于寄生虫对传统药物的耐药性，寻找新的抗疟化疗变得越来越紧迫。三恶喹是合成的杂合分子，含有三恶烷基序（其负责青蒿素的抗疟疾活性）连接到氨基喹啉实体（其负责氯喹的抗疟原虫特性）。这些三恶喹对恶性疟原虫的幼红细胞期具有高度效力，并在体外对恶性疟原虫的氯喹敏感和抗性菌株表现出有效的活性（50%抑制浓度，4至32 nM），并且在抑制性和治愈性小鼠试验中对长春疟原虫和约氏疟原虫尼日利亚亚种也具有体内活性。Trioxaquine DU 1302是这些有前途的抗疟药之一。本研究证实了该药物对细胞系和小鼠模型没有毒性。此外，DU 1302对配子体（由蚊子传播的形式）表现出有效的活性，因为杀死配子体对于限制疟疾的传播至关重要。这种三恶喹原型的化学合成的容易性应被认为是一个额外的优势，并且将使这些药物负担得起而不干扰药物供应。
Malaria is the third most significant cause of infectious disease in the world. The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to classical drugs. Trioxaquines are synthetic hybrid molecules containing a trioxane motif (which is responsible for the antimalarial activity of artemisinin) linked to an aminoquinoline entity (which is responsible for the antiplasmodial properties of chloroquine). These trioxaquines are highly potent against young erythrocytic stages of Plasmodium falciparum and exhibit efficient activity in vitro against chloroquine-sensitive and -resistant strains of P. falciparum (50% inhibitory concentration, 4 to 32 nM) and are also active in vivo against P. vinckei petteri and P. yoelii nigeriensis in suppressive and curative murine tests. The trioxaquine DU1302 is one of these promising antimalarial agents. The present study confirms the absence of toxicity of this drug on cell lines and in a mice model. Moreover, DU1302 exhibits potent activity against gametocytes, the form transmitted by mosquitoes, as killing of the gametocytes is essential to limit the spread of malaria. The ease of chemical synthesis of this trioxaquine prototype should be considered an additional advantage and would make these drugs affordable without perturbations of the drug supply.