Structure-Based Drug Design of PfDHODH Inhibitors as Antimalarial Agents

Part of the Challenges and Advances in Computational Chemistry and Physics book series (COCH, volume 27)


Structure-based drug design (SBDD) is being efficiently used for the design of antimalarial agents. It is a very effective tool for challenges like drug selectivity and resistance. Over the past decade, a considerable number of druggable targets have been explored—these include Na+ ATPase 4 ion channel, cytochrome bc1, mitochondrial electron transport chain, phosphatidylinositol 4-kinase (PfPI4 K), dihydroorotate dehydrogenase, hemozoin formation, dihydrofolate reductase inhibitors, etc. Among these, Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is a new and very promising target. PfDHODH has shown considerable potential in arresting growth of the parasite at blood stage by inhibiting pyrimidine biosynthesis. This chapter provides a review of all the SBDD efforts for the development of inhibitors against PfDHODH.


Plasmodium falciparum Structure-based drug design Molecular docking Virtual screening Dihydroorotate dehydrogenase Selectivity 

List of Abbreviations


Aspartate carbamoyltransferase


Absorption, distribution, metabolism, and excretion


Comparative molecular field analysis


Comparative molecular similarity index analysis


Coenzyme Q (Ubiquinone)


Cytidine triphosphate


Docking-based pharmacophore






Dihydroorotate dehydrogenase


Deoxyribose thymidine monophosphate

E. coli.

Escherichia coli


Flavin adenine dinucleotide


Flavin mononucleotide


Genetic partial least squares


Glutamine amidotransferase/carbamoyl phosphate synthetase




Molecular mechanics/Generalized Born surface area


Molecular shape analysis


Multilinear regression


Nicotinamide adenine dinucleotide


Orotidine 5′-monophosphate decarboxylase


Orotate phosphoribosyltransferase








Plasmodium berghei


Protein Data Bank


Plasmodium falciparum




Quantitative structure–activity relationship


Root mean square


Ribonucleic Acid


Structure-based drug design


Support vector machine


Uridine monophosphate


Uridine triphosphate



The University Grants Commission is gratefully acknowledged for the financial support to Shweta Bhagat (UGC, Grant No. 43395). The authors thank Department of Science and Technology (DST), Government of India, New Delhi, India, for financial support.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medicinal ChemistryNational Institute of Pharmaceutical Education and Research (NIPER)S.A.S. NagarIndia
  2. 2.Department of PharmacoinformaticsNational Institute of Pharmaceutical Education and Research (NIPER)S.A.S. NagarIndia

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