Comparative study between 3D-QSAR and Docking-Based Pharmacophore models for potent Plasomodium falciparum dihydroorotate dehydrogenase inhibitors

Tien-Sheng Tseng, Yu-Ching Lee, Nai-Wan Hsiao, Yun-Ru Liu, Keng-Chang Tsai

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Malaria, caused by infections of the human malaria parasites Plasmodium falciparum, is a global infectious parasitic disease. Each year, about three million people died from malaria and the majority of whom are pregnant women and young children. Recently, a number of research attempt to reduce malaria parasite resistance and the toxicity of anti-malarial drugs. Nowadays, Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) was validated as a potent drug target to inhibit malarial activity by blocking pyrimidine biosynthesis. In this study, we employed 3D-QSAR Pharmacophore Generation and Docking-Based Pharmacophore Development to build the pharmacophore by using the collected 67 effective inhibitors against PfDHODH. 3D-QSAR Pharmacophore model, Hypo1, shows the high correlation coefficient (0.935), the lowest RMS deviation (2.15), the predicting accuracy of successful rates to training set (89.4%) and test set compounds (72.4%), respectively, revealing favorable predictive ability and is a reliable for further study. Additionally, Docking-Based Pharmacophore model, DBP-All255, exhibits comparable predictive capability to that of Hypo1, while DBP-Top1 shows poor statistical significance. This study reveals pharmacophore features of Hypo1, built by 3D-QSAR Pharmacophore Generation, are well-complementary to the functional residues in the active site of PfDHODH and is of great reliable for database screening. © 2015 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Issue number2
Publication statusPublished - 2016


  • 3D-QSAR Pharmacophore Generation
  • Catalyst
  • Docking-Based Pharmacophore Development
  • PfDHODH inhibitor
  • Pharmacophore
  • dihydroorotate dehydrogenase
  • dihydroorotate dehydrogenase inhibitor
  • accuracy
  • antimalarial activity
  • Article
  • correlation coefficient
  • drug potency
  • drug targeting
  • IC50
  • intermethod comparison
  • malaria
  • molecular docking
  • nonhuman
  • pharmacophore
  • Plasmodium falciparum
  • quantitative structure activity relation


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