Novel azaphilones, kasanosins A and B, which are specific inhibitors of eukaryotic DNA polymerases β and λ from Talaromyces sp.
- 作者：Takuma Kimura ; Masayuki Nishida ; Kouji Kuramochi ; Fumio Sugawara ; Hiromi Yoshida ; Yoshiyuki Mizushina
- 关键词：Kasanosin A ; Kasanosin B ; Azaphilone ; DNA polymerase β ; DNA polymerase λ ; Family X of DNA polymerases ; Enzyme inhibitor
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 April 2008
- 卷：16
- 期：8
- 页码：4594-4599
- 文件大小：1071 K
摘要
Kasanosins A (1) and B (2) are novel azaphilones isolated from cultures of Talaromyces sp. derived from seaweed, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited the activities of eukaryotic DNA polymerases β and λ (pols β and λ) in family X of pols, and compound 1 was a stronger inhibitor than compound 2. The IC50 values of compound 1 on rat pol β and human pol λ were 27.3 and 35.0 μM, respectively. On the other hand, compounds 1 and 2 did not influence the activities of terminal deoxynucleotidyl transferase (TdT), which is a pol of family X, and the other families of eukaryotic pols, such as family A (i.e., pol γ), family B (i.e., pols 
, δ, and ε) and family Y (i.e., pols η, ι, and κ), and showed no effect even on the activities of plant pol , fish pol δ, prokaryotic pols, and other DNA metabolic enzymes, such as calf primase of pol , human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse inosine 5′-monophosphate (IMP) dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase, and bovine deoxyribonuclease I. The results suggested that these novel compounds could identify the inhibition between pols β, λ, and TdT in family X.
, δ, and ε) and family Y (i.e., pols η, ι, and κ), and showed no effect even on the activities of plant pol , fish pol δ, prokaryotic pols, and other DNA metabolic enzymes, such as calf primase of pol , human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse inosine 5′-monophosphate (IMP) dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase, and bovine deoxyribonuclease I. The results suggested that these novel compounds could identify the inhibition between pols β, λ, and TdT in family X.