Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents.
Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents.
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DOI：
10.1016/j.bmc.2009.05.011
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发表时间：
2009-07-01
影响因子：
3.5
通讯作者：
Zeng, Yuling
中科院分区：
文献类型：
--
作者：
Zhu, Shuren;Zhang, Quan;Gudise, Chandrashekar;Wei, Lai;Smith, Erika;Zeng, Yuling
常山碱是从常山中分离得到的一种生物碱，是抗恶性疟原虫的有效成分。不良副作用已经排除了febrifugine作为一种潜在的临床药物。本研究设计并合成了新型的常山碱类似物。通过减少或消除形成化学反应性和毒性中间体和代谢物的趋势，实现了较低的毒性。评价合成化合物的急性毒性以及体外和体内抗疟功效。一些化合物的毒性比天然产物febrifugine和现有的抗疟疾药物氯喹小得多，预计具有广泛的治疗窗口。这些化合物，以及潜在的设计原理，可能会发现有用的发现和开发新的抗疟疾药物。
Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum. Adverse side effects have precluded febrifugine as a potential clinical drug. In this study novel febrifugine analogues were designed and synthesized. Lower toxicity was achieved by reducing or eliminating the tendency of forming chemically reactive and toxic intermediates and metabolites. Synthesized compounds were evaluated for acute toxicity and in vitro and in vivo antimalarial efficacy. Some compounds are much less toxic than the natural product febrifugine and existing antimalarial drug chloroquine and are expected to possess wide therapeutic windows. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs.
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影响因子：
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