Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases

Takuma Kimura, Toshifumi Takeuchi, Yuko Kumamoto-Yonezawa, Eiji Ohashi, Haruo Ohmori, Chikahide Masutani, Fumio Hanaoka, Fumio Sugawara, Hiromi Yoshida, Yoshiyuki Mizushina

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols η, ι and κ), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol ι activity was most strongly inhibited by compounds 1 and 2, with IC50 values of 19.8 and 32.5 μM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ε) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.

Original languageEnglish
Pages (from-to)1811-1816
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number5
DOIs
Publication statusPublished - Mar 1 2009
Externally publishedYes

Fingerprint

Polynucleotide 5'-Hydroxyl-Kinase
DNA Primase
Type II DNA Topoisomerase
Type I DNA Topoisomerase
DNA Nucleotidylexotransferase
Telomerase
Deoxyribonuclease I
DNA-Directed DNA Polymerase
Fungi
Bryophyta
Penicillium
DNA
Enzymes
Oceans and Seas
Inhibitory Concentration 50
HIV-1
Human immunodeficiency virus 1 reverse transcriptase
bacteriophage T7 RNA polymerase
penicilliol A
penicilliol B

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Kimura, T., Takeuchi, T., Kumamoto-Yonezawa, Y., Ohashi, E., Ohmori, H., Masutani, C., ... Mizushina, Y. (2009). Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. Bioorganic and Medicinal Chemistry, 17(5), 1811-1816. https://doi.org/10.1016/j.bmc.2009.01.064

Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. / Kimura, Takuma; Takeuchi, Toshifumi; Kumamoto-Yonezawa, Yuko; Ohashi, Eiji; Ohmori, Haruo; Masutani, Chikahide; Hanaoka, Fumio; Sugawara, Fumio; Yoshida, Hiromi; Mizushina, Yoshiyuki.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 5, 01.03.2009, p. 1811-1816.

Research output: Contribution to journalArticle

Kimura, T, Takeuchi, T, Kumamoto-Yonezawa, Y, Ohashi, E, Ohmori, H, Masutani, C, Hanaoka, F, Sugawara, F, Yoshida, H & Mizushina, Y 2009, 'Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases', Bioorganic and Medicinal Chemistry, vol. 17, no. 5, pp. 1811-1816. https://doi.org/10.1016/j.bmc.2009.01.064
Kimura, Takuma ; Takeuchi, Toshifumi ; Kumamoto-Yonezawa, Yuko ; Ohashi, Eiji ; Ohmori, Haruo ; Masutani, Chikahide ; Hanaoka, Fumio ; Sugawara, Fumio ; Yoshida, Hiromi ; Mizushina, Yoshiyuki. / Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 5. pp. 1811-1816.
@article{016dcf1d1b2b44b1a0584e66d3747301,
title = "Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases",
abstract = "Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols η, ι and κ), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol ι activity was most strongly inhibited by compounds 1 and 2, with IC50 values of 19.8 and 32.5 μM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ε) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.",
author = "Takuma Kimura and Toshifumi Takeuchi and Yuko Kumamoto-Yonezawa and Eiji Ohashi and Haruo Ohmori and Chikahide Masutani and Fumio Hanaoka and Fumio Sugawara and Hiromi Yoshida and Yoshiyuki Mizushina",
year = "2009",
month = "3",
day = "1",
doi = "10.1016/j.bmc.2009.01.064",
language = "English",
volume = "17",
pages = "1811--1816",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases

AU - Kimura, Takuma

AU - Takeuchi, Toshifumi

AU - Kumamoto-Yonezawa, Yuko

AU - Ohashi, Eiji

AU - Ohmori, Haruo

AU - Masutani, Chikahide

AU - Hanaoka, Fumio

AU - Sugawara, Fumio

AU - Yoshida, Hiromi

AU - Mizushina, Yoshiyuki

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols η, ι and κ), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol ι activity was most strongly inhibited by compounds 1 and 2, with IC50 values of 19.8 and 32.5 μM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ε) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.

AB - Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols η, ι and κ), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol ι activity was most strongly inhibited by compounds 1 and 2, with IC50 values of 19.8 and 32.5 μM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ε) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.

UR - http://www.scopus.com/inward/record.url?scp=61349196981&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61349196981&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2009.01.064

DO - 10.1016/j.bmc.2009.01.064

M3 - Article

VL - 17

SP - 1811

EP - 1816

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 5

ER -