Iron chelators as anti-infectives; malaria as a paradigm
Iron chelators as anti-infectives; malaria as a paradigm
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DOI：
10.1111/j.1574-695x.1999.tb01401.x
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发表时间：
1999-12-01
影响因子：
--
通讯作者：
Gordeuk, VR
中科院分区：
文献类型：
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作者：
Cabantchik, ZI;Moody-Haupt, S;Gordeuk, VR
疟疾是威胁生命的主要寄生虫病，也是全球公共卫生问题的根源。媒介根除计划的失败以及耐药寄生虫的出现和传播对开发有效、安全和负担得起的抗疟疾药物提出了紧迫的挑战。此类药物的设计很大程度上基于将药物靶向用于宿主消化的寄生虫机器和血红蛋白分解代谢的产物。铁螯合剂通过剥夺细胞内寄生虫必需的铁来选择性抑制寄生虫的生长。然而，通过作用于寄生虫受损的巨噬细胞，螯合剂还可以加速吞噬作用的恢复和寄生虫的消除。为了在临床上有效，螯合剂需要在血液中保留很长时间。治疗剂量可以通过适当的药物组合和制剂或递送装置来获得，并且这些必须以宿主良好耐受的形式提供。早期文献表明螯合疗法具有对抗人类疟疾的活性，这为设计基于短期缺铁的新颖且更有效的疗法铺平了道路。 (C) 1999 年由 Elsevier Science B.V. 出版。保留所有权利。
Malaria is the major life threatening parasitic disease and the cause of a global public health problem. The failure of vector eradication programs and the appearance and spread of drug resistant parasites have posed the urgent challenge of developing effective, safe and affordable anti-malarial drugs. The design of such drugs is largely based on the targeting of agents to the parasite-based machinery for host digestion and to the products of hemoglobin catabolism. Iron chelators, by depriving intracellular parasites from essential iron, lead to selective suppression of parasite growth. However, by acting on parasite-impaired macrophages, chelators can also expedite resumption of phagocytosis and elimination of parasites. In order to be clinically effective, chelators need to be maintained in the blood for extensive time periods. Therapeutic doses can be attained with appropriate drug combinations and formulations or delivery devices and these must be presented in a form well tolerated by the host. The early documentation that chelation therapy has activity against human malaria has paved the road for the design of novel and more efficient remedies based on short-term iron deprivation. (C) 1999 Published by Elsevier Science B.V. All rights reserved.