Novel azaphilones, kasanosins A and B, which are specific inhibitors of eukaryotic DNA polymerases β and λ from Talaromyces sp.

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 α, δ, and ε) and family Y (i.e., pols η, ι, and κ), and showed no effect even on the activities of plant pol α, fish pol δ, 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 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.

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 in family X of pols.Figure optionsDownload as PowerPoint slide