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Coptisine, a natural alkaloid from Coptidis Rhizoma , inhibits plasmodium falciparum dihydroorotate dehydrogenase
Author(s) -
Lang Li,
Hu Qian,
Wang Jingyuan,
Liu Zehui,
Huang Jin,
Lu Weiqiang,
Huang Ying
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13197
Subject(s) - coptisine , dihydroorotate dehydrogenase , alkaloid , ic50 , docking (animal) , pharmacology , chemistry , traditional medicine , palmatine , biology , biochemistry , stereochemistry , enzyme , in vitro , medicine , nursing
Plasmodium falciparum dihydroorotate dehydrogenase (Pf DHODH ) is a promising drug target for antimalarial chemotherapy. In our continuous efforts to develop more potent Pf DHODH inhibitors, a unique library of active ingredients from traditional Chinese medicine ( TCM ) has been collected and was screened in this study. Through the initial screening, we found that coptisine, a natural alkaloid from TCM Coptidis Rhizoma , was a novel and potent inhibitor of Pf DHODH with an IC 50 value of 1.83 ± 0.08 μ m . At the same time, enzyme kinetic analysis using Lineweaver‐Burk plot indicated that coptisine is an uncompetitive inhibitor for Pf DHODH . Thermal shift assay and molecular docking simulation research reveal that coptisine is capable of binding with Pf DHODH . Moreover, coptisine exhibits weak inhibition activity against human DHODH , indicating that coptisine is a selective inhibitor of Pf DHODH . Taken together, our study highlights the potential of active ingredients in TCM as valuable resource for discovering novel chemical scaffolds for Pf DHODH .