Synthesis and antimalarial activity of novel dihydro-artemisinin derivatives |
| |
Authors: | Liu Yang Cui Kunqiang Lu Weiqiang Luo Wei Wang Jian Huang Jin Guo Chun |
| |
Affiliation: | Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. syphuly0325@yahoo.com.cn |
| |
Abstract: | The Plasmodium falciparum cysteine protease falcipain-2, one of the most promising targets for antimalarial drug design, plays a key role in parasite survival as a major peptide hydrolase within the hemoglobin degradation pathway. In this work, a series of novel dihydroartemisinin derivatives based on (thio)semicarbazone scaffold were designed and synthesized as potential falcipain-2 inhibitors. The in vitro biological assay indicated that most of the target compounds showed excellent inhibition activity against P. falciparum falcipain-2, with IC(50) values in the 0.29-10.63 μM range. Molecular docking studies were performed to investigate the binding affinities and interaction modes for the inhibitors. The preliminary SARs were summarized and could serve as a foundation for further investigation in the development of antimalarial drugs. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|