Gentisyl alcohol and homogentisic acid: Plasmodium falciparum dihydroorotate dehydrogenase inhibitors isolated from fungi

Amila Pramisandi; Kesi Kurnia; Evita Chrisnayanti; Putri Bernawati; Kazuyuki Dobashi; Mihoko Mori; Anis Herliyati Mahsunah; Kenichi Nonaka; Atsuko Matsumoto; Kristiningrum; Dyah Noor Hidayati; Diana Dewi; Erwahyuni Endang Prabandari; Eri Amalia; Yulia Rahmawati; Arif Nurkanto; Daniel Ken Inaoka; Danang Waluyo; Kiyoshi Kita; Tomoyoshi Nozaki; Satoshi Ōmura; Kazuro Shiomi

doi:10.2323/jgam.2020.08.004

Short Communications

Gentisyl alcohol and homogentisic acid: Plasmodium falciparum dihydroorotate dehydrogenase inhibitors isolated from fungi

Amila Pramisandi, Kesi Kurnia, Evita Chrisnayanti, Putri Bernawati, Kazuyuki Dobashi, Mihoko Mori, Anis Herliyati Mahsunah, Kenichi Nonaka, Atsuko Matsumoto, Kristiningrum, Dyah Noor Hidayati, Diana Dewi, Erwahyuni Endang Prabandari, Eri Amalia, Yulia Rahmawati, 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)
Kesi Kurnia
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Evita Chrisnayanti
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Putri Bernawati
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
Anis Herliyati Mahsunah
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
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
Kristiningrum
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Dyah Noor Hidayati
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Diana Dewi
Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT)
Erwahyuni Endang Prabandari
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
Yulia Rahmawati
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
Department of Host-Defense Biochemistry, 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, inhibitor, malaria, Plasmodium falciparum

JOURNAL FREE ACCESS

2021 Volume 67 Issue 3 Pages 114-117

DOI https://doi.org/10.2323/jgam.2020.08.004

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Abstract

Two Indonesian fungi Aspergillus assiutensis BioMCC-f.T.7495 and Penicillium pedernalense BioMCC-f.T.5350 along with a Japanese fungus Hypomyces pseudocorticiicola FKI-9008 have been found to produce gentisyl alcohol (1), which inhibits Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) with an IC₅₀ value of 3.4 μM. Another Indonesian fungus, Penicillium citrinum BioMCC-f.T.6730, produced an analog of 1, homogentisic acid (4), which also inhibits PfDHODH with an IC₅₀ value of 47.6 μM.

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