Microbial inhibitors active against Plasmodium falciparum dihydroorotate dehydrogenase derived from an Indonesian soil fungus, Talaromyces pinophilus BioMCC-f.T.3979

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

doi:10.2323/jgam.2019.11.007

This article has now been updated. Please use the final version.

Microbial inhibitors active against Plasmodium falciparum dihydroorotate dehydrogenase derived from an Indonesian soil fungus, Talaromyces pinophilus BioMCC-f.T.3979

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

Author information

Amila Pramisandi
Graduate School of Infection Control Sciences, Kitasato University
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Kazuyuki Dobashi
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences
Mihoko Mori
Graduate School of Infection Control Sciences, Kitasato University
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences
Kenichi Nonaka
Graduate School of Infection Control Sciences, Kitasato University
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences
Atsuko Matsumoto
Graduate School of Infection Control Sciences, Kitasato University
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences
Toshiyuki Tokiwa
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences
Mayuka Higo
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences
Kristiningrum
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Eri Amalia
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo
Arif Nurkanto
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo
Research Center for Biology, Indonesia Institute of Sciences (LIPI)
Daniel Ken Inaoka
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo
School of Tropical Medicine and Global Health, Nagasaki University
Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University
Danang Waluyo
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Kiyoshi Kita
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo
School of Tropical Medicine and Global Health, Nagasaki University
Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University
Tomoyoshi Nozaki
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo
Satoshi Ōmura
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences
Kazuro Shiomi
Graduate School of Infection Control Sciences, Kitasato University
Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences

Keywords: dihydroorotate dehydrogenase, malaria, Plasmodium falciparum, Talaromyces pinophilus

JOURNAL FREE ACCESS Advance online publication

Article ID: 2019.11.007

DOI https://doi.org/10.2323/jgam.2019.11.007

The final version of this article is now available: Vol. 66 (2020), No. 5 pp. 273-278

Details

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.

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