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

  • J Gen Appl Microbiol. 2021 Jul 31;67(3):114-117. doi: 10.2323/jgam.2020.08.004.
Amila Pramisandi  1  2 Kesi Kurnia  2 Evita Chrisnayanti  2 Putri Bernawati  2 Kazuyuki Dobashi  3 Mihoko Mori  1  3 Anis Herliyati Mahsunah  2 Kenichi Nonaka  1  3 Atsuko Matsumoto  1  3 Kristiningrum  2 Dyah Noor Hidayati  2 Diana Dewi  2 Erwahyuni Endang Prabandari  2 Eri Amalia  4 Yulia Rahmawati  4 Arif Nurkanto  4  5 Daniel Ken Inaoka  4  6  7 Danang Waluyo  2 Kiyoshi Kita  4  6  7  8 Tomoyoshi Nozaki  4 Satoshi Ōmura  3 Kazuro Shiomi  1  3
Affiliations
  • 1. Graduate School of Infection Control Sciences, Kitasato University.
  • 2. Laboratory for Biotechnology, Agency for the Assessment and Application of Technology (BPPT).
  • 3. Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences.
  • 4. Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo.
  • 5. Research Center for Biology, Indonesia Institute of Sciences (LIPI).
  • 6. School of Tropical Medicine and Global Health, Nagasaki University.
  • 7. Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University.
  • 8. Department of Host-Defense Biochemistry, Institute of Tropical Medicine (NEKKEN), Nagasaki University.
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.

Keywords
Plasmodium falciparum; dihydroorotate dehydrogenase; inhibitor; malaria.
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