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 IC50 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: falcipain-2 inhibitors; dihydroartemisinin derivatives; inhibition activity; molecular docking studies; SARs
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Liu, Y.; Cui, K.; Lu, W.; Luo, W.; Wang, J.; Huang, J.; Guo, C. Synthesis and Antimalarial Activity of Novel Dihydro-Artemisinin Derivatives. Molecules 2011, 16, 4527-4538.
Liu Y, Cui K, Lu W, Luo W, Wang J, Huang J, Guo C. Synthesis and Antimalarial Activity of Novel Dihydro-Artemisinin Derivatives. Molecules. 2011; 16(6):4527-4538.
Liu, Yang; Cui, Kunqiang; Lu, Weiqiang; Luo, Wei; Wang, Jian; Huang, Jin; Guo, Chun. 2011. "Synthesis and Antimalarial Activity of Novel Dihydro-Artemisinin Derivatives." Molecules 16, no. 6: 4527-4538.