螺环吲哚酮候选药物 NITD609 能够强效抑制配子体形成，并阻止恶性疟原虫传播给疟蚊媒介。
The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.
机构信息
Medical Microbiology Department, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
出版信息
Antimicrob Agents Chemother. 2012 Jul;56(7):3544-8. doi: 10.1128/AAC.06377-11. Epub 2012 Apr 16.
Abstract
The global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite of in vitro assays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development of Plasmodium falciparum gametocytes in vitro in a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to the Anopheles stephensi mosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against different P. falciparum transmission stages.
摘要
全球疟疾议程已经从控制临床病例重新定位为彻底消除疟疾。为此，一个关键目标是阻断疟原虫从人类向蚊子传播。评估了新型抗疟药物候选物 NITD609 的减传潜力，并与几种已确立的抗疟药物（青蒿琥酯、甲氟喹、阿莫地喹）进行了比较，使用了一系列体外检测方法。通过使用显微镜读数，发现 NITD609 在 5 至 500 nM 的范围内以剂量依赖的方式抑制恶性疟原虫配子体的早期和晚期体外发育。此外，使用标准的膜喂养检测方法，还发现 NITD609 是一种非常有效的药物，可以减少向疟蚊传播。总的来说，我们的数据表明 NITD609 对不同的恶性疟原虫传播阶段具有很强的减传作用。
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