Abstract
The de novo molecular design program SPROUT has been applied to the X-ray crystal structures of Plasmodium and human dihydroorotate dehydrogenase, respectively. The resulting design templates were used to prepare a series of molecules which, in keeping with predictions, showed useful levels of species-selective enzyme inhibition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimalarials / chemical synthesis*
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Antimalarials / pharmacology
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Catalysis
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Chemistry, Pharmaceutical / methods*
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Computer Simulation
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Crystallography, X-Ray
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Dihydroorotate Dehydrogenase
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Drug Design*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Kinetics
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Models, Chemical
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Models, Molecular
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Molecular Conformation
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Oxidoreductases Acting on CH-CH Group Donors / chemistry*
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Plasmodium falciparum / enzymology*
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Protein Conformation
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Software
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Substrate Specificity
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Ubiquinone / chemistry
Substances
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Antimalarials
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Dihydroorotate Dehydrogenase
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Enzyme Inhibitors
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Ubiquinone
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Oxidoreductases Acting on CH-CH Group Donors