title: Nanomolar Antimalarial Agents against Chloroquine-Resistant Plasmodium falciparum from Medicinal Plants and Their Structure-Activity Relationships.
abstract: Inspired by the discovery of the antimalarial drug artemisinin from a traditional Chinese medicine (TCM), a natural product library of 44 lindenane-type sesquiterpenoids was assessed for activities against the Dd2 chloroquine-resistant strain of the malaria parasite Plasmodium falciparum. These compounds were mainly isolated from plants of the Chloranthus genus, many species of which are named "Sikuaiwa" in TCM and have long been used to treat malaria. The compounds consisted of 41 sesquiterpenoid dimers and three monomers, including the 12 new dimers 1-12 isolated from Chloranthus fortunei. The results showed that 16 dimers exhibited potent antiplasmodial activities (<100 nM); in particular, compounds 1, 14, and 19 exhibited low nanomolar activities with IC50values ranging from 1 to 7 nM, which is comparable to the potency of artemisinin, and selectivity index values toward mammalian cells greater than 500. A comprehensive structure-activity relationship study indicated that three functional groups are essential and two motifs can be modified.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Seema
authors.initials: S
authors.lastname: Dalal
authors.forename: Emilio F
authors.initials: EF
authors.lastname: Merino
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
authors.forename: Qun-Fang
authors.initials: QF
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: David G I
authors.identifier: 0000-0001-8944-246X
authors.initials: DG
authors.lastname: Kingston
authors.forename: Maria B
authors.initials: MB
authors.lastname: Cassera
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
authors.forename: Jian-Min
authors.identifier: 0000-0002-4053-4870
authors.initials: JM
authors.lastname: Yue
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry*; D002738:Chloroquine / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D019684:Magnoliopsida / Q000737:chemistry*; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002738:Chloroquine; C031327:artemisinin