Microbial inhibitors active against plasmodium falciparum dihydroorotate dehydrogenase derived from an indonesian soil fungus, talaromyces pinophilus biomcc-f.T.3979

Abstract

An Indonesian soil fungus, Talaromyces pinophilus BioMCC-f.T.3979 was cultured to find novel scaf-folds of Plasmodium falciparum dihydroorotate de-hydrogenase (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.