新型FR-900098类似物作为强效恶性疟原虫1-脱氧-D-木酮糖-5-磷酸还原异构酶（Dxr）抑制剂的结构导向设计与生物合成
Structure-guided design and biosynthesis of a novel FR-900098 analogue as a potent Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr) inhibitor.
作者信息
Cobb Ryan E, Bae Brian, Li Zhi, DeSieno Matthew A, Nair Satish K, Zhao Huimin
机构信息
Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801, USA.
出版信息
Chem Commun (Camb). 2015 Feb 14;51(13):2526-8. doi: 10.1039/c4cc09181g.
Abstract
We report here the enzymatic biosynthesis of FR-900098 analogues and establish an in vivo platform for the biosynthesis of an N-propionyl derivative FR-900098P. FR-900098P is found to be a significantly more potent inhibitor of Plasmodium falciparum 1-deoxy-D-xylulose 5-phosphate reductoisomerase (PfDxr) than the parent compound, and thus a more promising antimalarial drug candidate.
摘要
我们在此报告FR-900098类似物的酶促生物合成，并建立了一个用于生物合成N-丙酰基衍生物FR-900098P的体内平台。研究发现，FR-900098P对恶性疟原虫1-脱氧-D-木酮糖5-磷酸还原异构酶（PfDxr）的抑制作用比母体化合物显著更强，因此是一个更有前景的抗疟药物候选物。
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