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3-O-methylfunicone, a Selective Inhibitor of Mammalian Y-family DNA Polymerases From an Australian Sea Salt Fungal Strain

3-O-methylfunicone, a Selective Inhibitor of Mammalian Y-family DNA Polymerases From an Australian Sea Salt Fungal Strain

Yoshiyuki Mizushina, Hirohisa Motoshima, Yasuhiro Yamaguchi, Toshifumi Takeuchi, Ken Hirano, Fumio Sugawara, Hiromi Yoshida

Mar Drugs. 2009 Nov 23;7(4):624-39.

PMID: 20098603

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 eta, iota and kappa). Among these pols, human pol kappa activity was most strongly inhibited, with an IC(50) value of 12.5 microM. On the other hand, the compound barely influenced the activities of the other families of mammalian pols, such as A-family (i.e., pol gamma), B-family (i.e., pols alpha, delta and epsilon) or X-family (i.e., pols beta, lambda and terminal deoxynucleotidyl transferase), and showed no effect on the activities of fish pol delta, plant pols, prokaryotic pols and other DNA metabolic enzymes, such as calf primase of pol alpha, 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415137	Inosine Monophosphate Dehydrogenase Type II human			Price

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