Parallel synthesis and antimalarial screening of a 4-aminoquinoline library
Parallel synthesis and antimalarial screening of a 4-aminoquinoline library
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DOI：
10.1021/cc0340473
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发表时间：
2004-05-01
影响因子：
--
通讯作者：
Guy, RK
中科院分区：
文献类型：
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作者：
Madrid, PB;Wilson, NT;Guy, RK
由于抗药性问题日益严重，迫切需要新的、具有成本效益的疟疾治疗药物。4-氨基喹啉提供了许多有用的抗疟药，而恶性疟原虫（最致命的人类疟疾形式的病原体）通常对这些药物缓慢产生耐药性。因此，喹啉的多样性筛选文库继续用于抗疟药物发现。我们在此报告了一种有效的方法，用于产生在分子的侧链部分的4-氨基喹啉变体的文库的发展。通过筛选该文库的抗恶性疟原虫活性来评估这些取代的效果，揭示了对耐药菌株具有活性的四种有效化合物。
Due to growing problems with drug resistance, there is an outstanding need for new, cost-effective drugs for the treatment of malaria. The 4-aminoquinolines have provided a number of useful antimalarials, and Plasmodium falciparum, the causative organism for the most deadly form of human malaria, is generally slow to develop resistance to these drugs. Therefore, diverse screening libraries of quinolines continue to be useful for antimalarial drug discovery. We report herein the development of an efficient method for producing libraries of 4-aminoquinolines variant in the side chain portion of the molecule. The effects of these substitutions were evaluated by screening this library for activity against P. falciparum, revealing four potent compounds active against drug-resistant strains.