青蒿素（青蒿琥酯）与血红素相互作用的分子模拟研究：抗疟药物与其假定受体之间的对接

Molecular modeling studies of the artemisinin (qinghaosu)-hemin interaction: docking between the antimalarial agent and its putative receptor.

作者信息

Shukla K L, Gund T M, Meshnick S R

机构信息

Department of Chemistry and Chemical Engineering, New Jersey Institute of Technology, Newark 07102, USA.

出版信息

J Mol Graph. 1995 Aug;13(4):215-22. doi: 10.1016/0263-7855(94)00001-9.

DOI:10.1016/0263-7855(94)00001-9

PMID:8527414

Abstract

Artemisinin (qinghaosu, QHS) is a promising new antimalarial agent that is effective against drug-resistant strains of malaria. The antimalarial activity of this drug appears to be mediated by an interaction of the drug's endoperoxide bridge with intraparasitic hemin. We have carried out a computer-assisted docking of QHS with hemin from various starting configurations and found that, in the most stable docked configuration, the endoperoxide bridge is in close proximity to the hemin iron. In contrast, an inactive analog, deoxyartemisinin (DQHS), docks in a different manner. Further computer analysis of the drug-hemin interaction might aid in the design of new QHS congeners.

摘要

青蒿素（青蒿琥酯，QHS）是一种有前景的新型抗疟药物，对耐药疟原虫菌株有效。该药物的抗疟活性似乎是由其过氧桥与寄生体内血红素的相互作用介导的。我们从各种起始构型对QHS与血红素进行了计算机辅助对接，发现，在最稳定的对接构型中，过氧桥与血红素铁紧密相邻。相比之下，无活性类似物脱氧青蒿素（DQHS）的对接方式不同。对药物 - 血红素相互作用的进一步计算机分析可能有助于设计新的青蒿素类似物。