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 language | English |
|---|---|
| Pages (from-to) | 1811-1816 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 17 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 1 2009 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
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 journal › Article
}
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
C2 - 19223184
AN - SCOPUS:61349196981
VL - 17
SP - 1811
EP - 1816
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 5
ER -