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

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. Epub 2021 Apr 2.

Authors

Amila Pramisandi^{1

2}, Kesi Kurnia², Evita Chrisnayanti², Putri Bernawati², Kazuyuki Dobashi³, Mihoko Mori^{1

3}, Anis Herliyati Mahsunah², Kenichi Nonaka^{1

3}, Atsuko Matsumoto^{1

3}, Kristiningrum², Dyah Noor Hidayati², Diana Dewi², Erwahyuni Endang Prabandari², Eri Amalia⁴, Yulia Rahmawati⁴, Arif Nurkanto^{4

5}, Daniel Ken Inaoka^{4

6

7}, Danang Waluyo², Kiyoshi Kita^{4

6

7

8}, Tomoyoshi Nozaki⁴, Satoshi Ōmura³, 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.

PMID: 33814517
DOI: 10.2323/jgam.2020.08.004

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.

MeSH terms

Antimalarials / chemistry
Antimalarials / isolation & purification
Antimalarials / pharmacology
Benzyl Alcohols / chemistry
Benzyl Alcohols / isolation & purification
Benzyl Alcohols / pharmacology*
Dihydroorotate Dehydrogenase
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Fungi / chemistry*
Fungi / classification
Homogentisic Acid / chemistry
Homogentisic Acid / isolation & purification
Homogentisic Acid / pharmacology*
Inhibitory Concentration 50
Molecular Structure
Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
Plasmodium falciparum / drug effects
Plasmodium falciparum / enzymology*
Protozoan Proteins / antagonists & inhibitors

Substances

Antimalarials
Benzyl Alcohols
Dihydroorotate Dehydrogenase
Enzyme Inhibitors
Protozoan Proteins
Oxidoreductases Acting on CH-CH Group Donors
Homogentisic Acid
2,5-dihydroxybenzyl alcohol