Next-Generation Antimalarial Drugs: Hybrid Molecules as a New Strategy in Drug Design.
Next-Generation Antimalarial Drugs: Hybrid Molecules as a New Strategy in Drug Design.
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DOI：
10.1002/ddr.20345
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发表时间：
2010-02
影响因子：
3.8
通讯作者：
Ishih, Akira
中科院分区：
文献类型：
--
作者：
Muregi, Francis W.;Ishih, Akira
关键词：
疟疾是一种影响全球近40%人口的疾病，化疗仍然是其控制策略的主要手段。由于对大多数现有抗疟药物出现抗药性，全球疟疾形势日益恶化，因此需要寻找新的药物。最近的抗疟药物设计的一个合理的方法，其特征在于“共价生物疗法”涉及连接两个分子与个人的内在活性到一个单一的代理，从而包装成一个单一的杂交分子的双重活性。目前在这一领域的研究似乎赞同杂交分子作为下一代抗疟药物。如果杂合前药的选择性毒性可以在体内被证明在寄生虫的靶位点具有良好的生物利用度，则它将提供各种优点，包括剂量依从性、最小化的毒性、设计更好的药物组合的能力以及更便宜的临床前评价，同时实现延迟或规避抗性发展的最终目的。这篇综述主要集中在已经开发的几种杂交分子上，特别强调那些被认为具有很高的临床应用潜力的分子。药物开发研究71：20-32，2010年。© 2009 Wiley-Liss公司。
Malaria is a disease that affects nearly 40% of the global population, and chemotherapy remains the mainstay of its control strategy. The global malaria situation is increasingly being exacerbated by the emergence of drug resistance to most of the available antimalarials, necessitating search for novel drugs. A recent rational approach of antimalarial drug design characterized as “covalent bitherapy” involves linking two molecules with individual intrinsic activity into a single agent, thus packaging dual-activity into a single hybrid molecule. Current research in this field seems to endorse hybrid molecules as the next-generation antimalarial drugs. If the selective toxicity of hybrid prodrugs can be demonstrated in vivo with good bioavailability at the target site in the parasite, it would offer various advantages including dosage compliance, minimized toxicity, ability to design better drug combinations, and cheaper preclinical evaluation while achieving the ultimate object of delaying or circumventing the development of resistance. This review is focused on several hybrid molecules that have been developed, with particular emphasis on those deemed to have high potential for development for clinical use. Drug Dev Res 71: 20–32, 2010. © 2009 Wiley-Liss, Inc.
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