80. [a] Patel V, Booker M et al. (2008) Identification and characterization of small molecule
inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J Biol Chem
283:35078–35085; [b] Skerlj RT, Bastos CM et al. (2011) Optimization of potent inhibitors
of P. falciparum dihydroorotate dehydrogenase for the treatment of malaria. ACS Med Chem
Lett 2:708–713
81. Fritzson I, Bedingfield PTP et al (2011) N-substituted salicylamides as selective malaria
parasite dihydroorotate dehydrogenase inhibitors. Med Chem Comm 2:895–898
82. Zhu J, Han L et al (2015) Design, synthesis, X-ray crystallographic analysis, and biological
evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate
dehydrogenase. J Med Chem 58:1123–1139
83. Azeredo LFSP, Coutinho JP et al (2017) Evaluation of 7-arylaminopyrazolo [1,5-a]
pyrimidines as anti-Plasmodium falciparum, antimalarial, and Pf dihydroorotate dehydrogenase inhibitors. Eur J Med Chem 126:72–83
84. Xu M, Zhu J et al (2013) Novel selective and potent inhibitors of malaria parasite
dihydroorotate dehydrogenase: discovery and optimization of dihydrothiophenone derivatives. J Med Chem 56:7911–7924
85. Schneider G, Fechner U (2005) Computer-based de novo design of drug-like molecules. Nat
Rev Drug Discov 4:649
86. Gillet VJ, Newell W et al (1994) SPROUT: recent developments in the de novo design of
molecules. J Chem Inf Comput Sci 34:207–217
87. Gujjar R, Marwaha A et al (2009) Identification of a metabolically stable
triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity
in mice. J Med Chem 52:1864–1872
88. Gujjar R, El Mazouni F et al (2011) Lead optimization of aryl and aralkyl amine-based
triazolopyrimidine inhibitors of Plasmodium Falciparum dihydroorotate dehydrogenase with
antimalarial activity in mice. J Med Chem 54:3935–3949
89. Ojha PK, Roy K (2010) Chemometric modeling, docking and in silico design of
triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors as antimalarials. Eur J
Med Chem 45:4645–4656
90. Shah P, Kumar S, Tiwari S, Siddiqi MI (2012) 3D-QSAR studies of triazolopyrimidine
derivatives of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors using a
combination of molecular dynamics, docking, and genetic algorithm-based methods. J Chem
Biol 5:91–103
91. Desai KR, Shaikh MS, Coutinho EC (2011) Molecular modeling studies, synthesis and
biological evaluation of derivatives of N-phenylbenzamide as Plasmodium falciparum
dihydroorotate dehydrogenase (PfDHODH) inhibitors. Med Chem Res 20:321–332
92. Vyas VK, Parikh H, Ghate M (2013) 3D QSAR studies on 5-(2-methylbenzimidazol-1-yl)-Nalkylthiophene-2-carboxamide derivatives as P. falciparum dihydroorotate dehydrogenase
(PfDHODH) inhibitors. Med Chem Res 22:2235–2243
93. Wadood A, Zaheer-ulhaqb (2013) In silico identification of novel inhibitors against
Plasmodium falciparum dihydroorate dehydrogenase. J Mol Graphics Model 40:40–47
94. Tseng TS, Lee YC et al (2016) Comparative study between 3D-QSAR and docking-based
pharmacophore models for potent Plasomodium falciparum dihydroorotate dehydrogenase
inhibitors. Bioorg Med Chem Lett 26:265–271
95. Hou X, Chen X, Zhang M, Yan A (2016) QSAR study on the antimalarial activity of
Plasmodium falciparum dihydroorotate dehydrogenase (Pf DHODH) inhibitors. SAR QSAR
Environ Res 27:101–124
96. Pavadai E, El Mazouni F et al (2016) Identification of new human malaria parasite
Plasmodium falciparum dihydroorotate dehydrogenase inhibitors by pharmacophore and
structure-based virtual screening. J Chem Inf Model 56:548–562
220
S. Bhagat et al.
inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J Biol Chem
283:35078–35085; [b] Skerlj RT, Bastos CM et al. (2011) Optimization of potent inhibitors
of P. falciparum dihydroorotate dehydrogenase for the treatment of malaria. ACS Med Chem
Lett 2:708–713
81. Fritzson I, Bedingfield PTP et al (2011) N-substituted salicylamides as selective malaria
parasite dihydroorotate dehydrogenase inhibitors. Med Chem Comm 2:895–898
82. Zhu J, Han L et al (2015) Design, synthesis, X-ray crystallographic analysis, and biological
evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate
dehydrogenase. J Med Chem 58:1123–1139
83. Azeredo LFSP, Coutinho JP et al (2017) Evaluation of 7-arylaminopyrazolo [1,5-a]
pyrimidines as anti-Plasmodium falciparum, antimalarial, and Pf dihydroorotate dehydrogenase inhibitors. Eur J Med Chem 126:72–83
84. Xu M, Zhu J et al (2013) Novel selective and potent inhibitors of malaria parasite
dihydroorotate dehydrogenase: discovery and optimization of dihydrothiophenone derivatives. J Med Chem 56:7911–7924
85. Schneider G, Fechner U (2005) Computer-based de novo design of drug-like molecules. Nat
Rev Drug Discov 4:649
86. Gillet VJ, Newell W et al (1994) SPROUT: recent developments in the de novo design of
molecules. J Chem Inf Comput Sci 34:207–217
87. Gujjar R, Marwaha A et al (2009) Identification of a metabolically stable
triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity
in mice. J Med Chem 52:1864–1872
88. Gujjar R, El Mazouni F et al (2011) Lead optimization of aryl and aralkyl amine-based
triazolopyrimidine inhibitors of Plasmodium Falciparum dihydroorotate dehydrogenase with
antimalarial activity in mice. J Med Chem 54:3935–3949
89. Ojha PK, Roy K (2010) Chemometric modeling, docking and in silico design of
triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors as antimalarials. Eur J
Med Chem 45:4645–4656
90. Shah P, Kumar S, Tiwari S, Siddiqi MI (2012) 3D-QSAR studies of triazolopyrimidine
derivatives of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors using a
combination of molecular dynamics, docking, and genetic algorithm-based methods. J Chem
Biol 5:91–103
91. Desai KR, Shaikh MS, Coutinho EC (2011) Molecular modeling studies, synthesis and
biological evaluation of derivatives of N-phenylbenzamide as Plasmodium falciparum
dihydroorotate dehydrogenase (PfDHODH) inhibitors. Med Chem Res 20:321–332
92. Vyas VK, Parikh H, Ghate M (2013) 3D QSAR studies on 5-(2-methylbenzimidazol-1-yl)-Nalkylthiophene-2-carboxamide derivatives as P. falciparum dihydroorotate dehydrogenase
(PfDHODH) inhibitors. Med Chem Res 22:2235–2243
93. Wadood A, Zaheer-ulhaqb (2013) In silico identification of novel inhibitors against
Plasmodium falciparum dihydroorate dehydrogenase. J Mol Graphics Model 40:40–47
94. Tseng TS, Lee YC et al (2016) Comparative study between 3D-QSAR and docking-based
pharmacophore models for potent Plasomodium falciparum dihydroorotate dehydrogenase
inhibitors. Bioorg Med Chem Lett 26:265–271
95. Hou X, Chen X, Zhang M, Yan A (2016) QSAR study on the antimalarial activity of
Plasmodium falciparum dihydroorotate dehydrogenase (Pf DHODH) inhibitors. SAR QSAR
Environ Res 27:101–124
96. Pavadai E, El Mazouni F et al (2016) Identification of new human malaria parasite
Plasmodium falciparum dihydroorotate dehydrogenase inhibitors by pharmacophore and
structure-based virtual screening. J Chem Inf Model 56:548–562
220
S. Bhagat et al.