title: Synthesis and antimalarial activity of novel dihydro-artemisinin derivatives.
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.
authors.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
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Kunqiang
authors.initials: K
authors.lastname: Cui
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C039060:artenimol; D003546:Cysteine Endopeptidases; C416224:falcipain 2