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Mar. Drugs 2009, 7(4), 624-639; doi:10.3390/md7040624
Article

3-O-Methylfunicone, a Selective Inhibitor of Mammalian Y-Family DNA Polymerases from an Australian Sea Salt Fungal Strain

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Received: 12 October 2009; in revised form: 18 November 2009 / Accepted: 19 November 2009 / Published: 23 November 2009
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
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Abstract: We isolated a pol inhibitor from the cultured mycelia extract of a fungal strain isolated from natural salt from a sea salt pan in Australia, which was identified as 3-O-methylfunicone by spectroscopic analyses. This compound selectively inhibited the activities of mammalian Y-family DNA polymerases (pols) (i.e., pols η, ι and κ). Among these pols, human pol κ activity was most strongly inhibited, with an IC50 value of 12.5 μM. On the other hand, the compound barely influenced the activities of the other families of mammalian 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 showed no effect on the activities of fish pol δ, plant pols, prokaryotic pols and other 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. This compound also suppressed the growth of two cultured human cancer cell lines, HCT116 (colon carcinoma cells) and HeLa (cervix carcinoma cells), and UV-treated HeLa cells exhibited lower clonogenic survival in the presence of inhibitor.
Keywords: 3-O-methylfunicone; Y-family DNA polymerase; DNA polymerase κ; enzyme inhibitor; marine fungal strains; Australian sea salt; anti-cancer drug 3-O-methylfunicone; Y-family DNA polymerase; DNA polymerase κ; enzyme inhibitor; marine fungal strains; Australian sea salt; anti-cancer drug
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Mizushina, Y.; Motoshima, H.; Yamaguchi, Y.; Takeuchi, T.; Hirano, K.; Sugawara, F.; Yoshida, H. 3-O-Methylfunicone, a Selective Inhibitor of Mammalian Y-Family DNA Polymerases from an Australian Sea Salt Fungal Strain. Mar. Drugs 2009, 7, 624-639.

AMA Style

Mizushina Y, Motoshima H, Yamaguchi Y, Takeuchi T, Hirano K, Sugawara F, Yoshida H. 3-O-Methylfunicone, a Selective Inhibitor of Mammalian Y-Family DNA Polymerases from an Australian Sea Salt Fungal Strain. Marine Drugs. 2009; 7(4):624-639.

Chicago/Turabian Style

Mizushina, Yoshiyuki; Motoshima, Hirohisa; Yamaguchi, Yasuhiro; Takeuchi, Toshifumi; Hirano, Ken; Sugawara, Fumio; Yoshida, Hiromi. 2009. "3-O-Methylfunicone, a Selective Inhibitor of Mammalian Y-Family DNA Polymerases from an Australian Sea Salt Fungal Strain." Mar. Drugs 7, no. 4: 624-639.



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