Identification of novel falcipain-2 inhibitors as potential antimalarial agents through structure-based virtual screening.
The SPECS database was screened against falcipain-2 with two different docking methods to identify structurally diverse nonpeptidic inhibitors. Twenty-eight nonpeptidic molecules among 81 compounds tested were identified as potential inhibitors of falcipain-2. One of the inhibitors exhibited in vitro activity with an IC50 value of 2.4 microM. Furthermore, the similarity analysis has demonstrated that it is feasible to find novel diverse falcipain-2 inhibitors with similar steric shape through virtual screening of large-scale chemical libraries.
Li
Honglin
H
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Huang
Jin
J
Chen
Lili
L
Liu
Xiaofeng
X
Chen
Tong
T
Zhu
Jin
J
Lu
Weiqiang
W
Shen
Xu
X
Li
Jian
J
Hilgenfeld
Rolf
R
Jiang
Hualiang
H
D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D019992:Databases as Topic; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D003546:Cysteine Endopeptidases; C416224:falcipain 2