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Microbial inhibitors active against Plasmodium falciparum dihydroorotate dehydrogenase derived from an Indonesian soil fungus, Talaromyces pinophilus BioMCC-fT3979

J Gen Appl Microbiol. 2020;

Amila Pramisandi, Kazuyuki Dobashi, Mihoko Mori, Kenichi Nonaka, Atsuko Matsumoto, Toshiyuki Tokiwa, Mayuka Higo, Eri Amalia, Arif Nurkanto, Daniel Ken Inaoka, Danang Waluyo, Kiyoshi Kita, Tomoyoshi Nozaki, Satoshi ōmura, Kazuro Shiomi

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Gene Synthesis	… to code from amino acid residues 158 to 569 was con- structed and optimized for expression in Escherichia coli by GenScript, Japan?… Although the isolated PfDHODH inhibitors are cytotoxic, it may be possible to structurally modify them to synthesize derivatives with minimal or?…	Get A Quote

摘要

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 IC 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.