通过基于结构的虚拟筛选鉴定多种天然产物作为疟原虫蛋白酶-2抑制剂。
Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening.
作者信息
Wang Liyan, Zhang Shoude, Zhu Junsheng, Zhu Lili, Liu Xiaofeng, Shan Lei, Huang Jin, Zhang Weidong, Li Honglin
机构信息
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.
Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
出版信息
Bioorg Med Chem Lett. 2014 Mar 1;24(5):1261-4. doi: 10.1016/j.bmcl.2014.01.074. Epub 2014 Feb 2.
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.
通过基于结构的虚拟筛选，从我们内部的天然产物数据库中成功鉴定出10种天然化合物作为疟原虫蛋白酶-2（FP-2）抑制剂，它们对FP-2显示出中等抑制活性，IC50值范围为3.18至68.19μM。其中一种抑制剂（化合物5）在微摩尔范围内（对3D7细胞和Dd2细胞的IC50分别为5.54μM和4.05μM）对恶性疟原虫的氯喹敏感株（3D7）和氯喹耐药株（Dd2）也表现出体外抗疟原虫活性。此外，对预测的结合模式进行分析以解释构效关系，这将有助于进一步的结构修饰。
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