Tafenoquine: A Step toward Malaria Elimination.,Biochemistry

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Tafenoquine: A Step toward Malaria Elimination.
Biochemistry ( IF 2.9 ) Pub Date : 2020-02-24 , DOI: 10.1021/acs.biochem.9b01105
Kuan-Yi Lu ₁ , Emily R Derbyshire _{1,

2}

Affiliation

There is a pressing need for compounds with broad-spectrum activity against malaria parasites at various life cycle stages to achieve malaria elimination. However, this goal cannot be accomplished without targeting the tenacious dormant liver-stage hypnozoite that causes multiple relapses after the first episode of illness. In the search for the magic bullet to radically cure Plasmodium vivax malaria, tafenoquine outperformed other candidate drugs and was approved by the U.S. Food and Drug Administration in 2018. Tafenoquine is an 8-aminoquinoline that inhibits multiple life stages of various Plasmodium species. Additionally, its much longer half-life allows for single-dose treatment, which will improve the compliance rate. Despite its approval and the long-time use of other 8-aminoquinolines, the mechanisms behind tafenoquine's activity and adverse effects are still largely unknown. In this Perspective, we discuss the plausible underlying mechanisms of tafenoquine's antiparasitic activity and highlight its role as a cellular stressor. We also discuss potential drug combinations and the development of next-generation 8-aminoquinolines to further improve the therapeutic index of tafenoquine for malaria treatment and prevention.

中文翻译：

Tafenoquine：迈向消除疟疾的一步。

迫切需要在各个生命周期阶段具有对付疟原虫的广谱活性的化合物以消除疟疾。但是，如果不针对顽固的休眠期肝第一亚眠子症，这将是无法实现的，后者在疾病首发后会导致多次复发。在寻找能从根本上治愈间日疟原虫疟疾的灵丹妙药时，他芬喹优于其他候选药物，并于2018年获得美国食品和药物管理局的批准。他芬喹是8-氨基喹啉，可抑制多种疟原虫物种的多个生命周期。此外，其更长的半衰期允许单剂量治疗，这将提高依从性。尽管已获批准并长期使用其他8-氨基喹啉，但tafenoquine'背后的机制其活性和不良反应在很大程度上仍然未知。在本《观点》中，我们讨论了tafenoquine抗寄生虫活性的合理的潜在机制，并强调了其作为细胞应激源的作用。我们还讨论了潜在的药物组合以及下一代8-氨基喹啉的开发，以进一步提高用于预防和治疗疟疾的tafenoquine的治疗指数。

更新日期：2020-02-24

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