title: Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening.
abstract: Ten natural compounds are successfully identified as falcipain-2 (FP-2) inhibitors from our in-house natural products database using structure-based virtual screening, which show moderate inhibitory activities against FP-2 with IC50 values ranging from 3.18 to 68.19 μM. While one of the inhibitors (compound 5) also exhibits in vitro antiplasmodial activity against chloroquine sensitive strain (3D7) and chloroquine resistant strain (Dd2) of Plasmodium falciparum in the micromolar range (IC50s=5.54 μM and 4.05 μM against 3D7 cells and Dd2 cells, respectively). Furthermore, the predicted binding poses are analyzed to explain the structure-activity relationships, which will be helpful for further structural modifications.
authors: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Liyan
authors: L
authors: Wang
authors: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Shoude
authors: S
authors: Zhang
authors: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Junsheng
authors: J
authors: Zhu
authors: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Lili
authors: L
authors: Zhu
authors: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Xiaofeng
authors: X
authors: Liu
authors: Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Lei
authors: L
authors: Shan
authors: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: huangjin@ecust.edu.cn.
authors: Jin
authors: J
authors: Huang
authors: Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: wdzhangy@hotmail.com.
authors: Weidong
authors: W
authors: Zhang
authors: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: hlli@ecust.edu.cn.
authors: Honglin
authors: H
authors: Li
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D062105:Molecular Docking Simulation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D001688:Biological Products; D004791:Enzyme Inhibitors; D003546:Cysteine Endopeptidases; C416224:falcipain 2
keywords: Antimalarial drug; Falcipain-2 inhibitors; Natural products; Virtual screening