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 journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number2
DOIs
Publication statusPublished - 2016 Jan 15

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Quantitative Structure-Activity Relationship
Plasmodium falciparum
Malaria
Parasites
Parasitic Diseases
Falciparum Malaria
Biosynthesis
Antimalarials
Pharmaceutical Preparations
Communicable Diseases
Toxicity
Pregnant Women
Catalytic Domain
Screening
Databases
Infection
Research
dihydroorotate dehydrogenase

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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abstract = "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.",
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Comparative study between 3D-QSAR and Docking-Based Pharmacophore models for potent Plasomodium falciparum dihydroorotate dehydrogenase inhibitors. / Tseng, Tien Sheng; Lee, Yu Ching; Hsiao, Nai-Wan; Liu, Yun Ru; Tsai, Keng Chang.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 2, 15.01.2016, p. 265-271.

Research output: Contribution to journalArticle

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AU - Liu, Yun Ru

AU - Tsai, Keng Chang

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