Abstract
An Indonesian soil fungus, Talaromyces pinophilus BioMCC-f.T.3979 was cultured to find novel scaffolds of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. We obtained altenusin (1), which inhibits PfDHODH, with an IC50 value of 5.9 μM, along with other metabolites: mitorubrinol (2) and mitorubrinic acid (3). Compounds 1 and 2 inhibited PfDHODH but displayed no activity against the human orthologue. They also inhibited P. falciparum 3D7 cell growth in vitro. Compound 3 showed little PfDHODH inhibitory activity or cell growth inhibitory activity.
Keywords:
Plasmodium falciparum; Talaromyces pinophilus; dihydroorotate dehydrogenase; malaria.
MeSH terms
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Antimalarials / chemistry
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Antimalarials / isolation & purification
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Antimalarials / pharmacology*
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Benzoates / chemistry
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Benzoates / isolation & purification
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Benzoates / pharmacology
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / isolation & purification
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Biphenyl Compounds / pharmacology
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Cell Line
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Cell Survival / drug effects
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Dihydroorotate Dehydrogenase
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology
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Humans
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Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / enzymology
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Plasmodium falciparum / growth & development
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Protozoan Proteins / antagonists & inhibitors*
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Soil Microbiology
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Species Specificity
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Talaromyces / chemistry*
Substances
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Antimalarials
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Benzoates
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Biphenyl Compounds
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Dihydroorotate Dehydrogenase
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Enzyme Inhibitors
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Protozoan Proteins
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altenusin
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mitorubrinic acid
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Oxidoreductases Acting on CH-CH Group Donors
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mitorubrin