Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening

Liyan Wang; Shoude Zhang; Junsheng Zhu; Lili Zhu; Xiaofeng Liu; Lei Shan; Jin Huang; Weidong Zhang; Honglin Li

doi:10.1016/j.bmcl.2014.01.074

Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening

Liyan Wang
, Shoude Zhang
, Junsheng Zhu
, Lili Zhu
, Xiaofeng Liu
, Lei Shan
, Jin Huang^*
, Weidong Zhang
, Honglin Li

^*Corresponding author for this work

East China University of Science and Technology
Naval Medical University

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English
Pages (from-to)	1261-1264
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2014.01.074
State	Published - 1 Mar 2014
Externally published	Yes

Keywords

Antimalarial drug
Falcipain-2 inhibitors
Natural products
Virtual screening

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10.1016/j.bmcl.2014.01.074

Cite this

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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.",

keywords = "Antimalarial drug, Falcipain-2 inhibitors, Natural products, Virtual screening",

author = "Liyan Wang and Shoude Zhang and Junsheng Zhu and Lili Zhu and Xiaofeng Liu and Lei Shan and Jin Huang and Weidong Zhang and Honglin Li",

year = "2014",

month = mar,

day = "1",

doi = "10.1016/j.bmcl.2014.01.074",

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pages = "1261--1264",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening

AU - Wang, Liyan

AU - Zhang, Shoude

AU - Zhu, Junsheng

AU - Zhu, Lili

AU - Liu, Xiaofeng

AU - Shan, Lei

AU - Huang, Jin

AU - Zhang, Weidong

AU - Li, Honglin

PY - 2014/3/1

Y1 - 2014/3/1

N2 - 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.

AB - 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.

KW - Antimalarial drug

KW - Falcipain-2 inhibitors

KW - Natural products

KW - Virtual screening

UR - https://www.scopus.com/pages/publications/84894562193

U2 - 10.1016/j.bmcl.2014.01.074

DO - 10.1016/j.bmcl.2014.01.074

M3 - 文章

C2 - 24530004

AN - SCOPUS:84894562193

SN - 0960-894X

VL - 24

SP - 1261

EP - 1264

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 5

ER -

Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening

Abstract

Keywords

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