Novel anti-inflammatory compounds from Rubus sieboldii, triterpenoids, are inhibitors of mammalian DNA polymerases.

Abstract:

Two anti-inflammatory triterpenoids, tormentic acid (TA) and euscaphic acid (EA), were found from the plant Rubus sieboldii. These triterpenoids showed an inhibitory effect against enzymes involved in replication, such as calf DNA polymerase alpha (pol alpha) and rat DNA polymerase beta (pol beta). The IC50 values of TA and EA were 37 and 61 microM for pol alpha and 46 and 108 microM for pol beta, respectively. However, TA and EA did not influence the activities of plant DNA polymerases, DNA primase, human immunodeficiency virus type-1 reverse transcriptase, terminal deoxynucleotidyl transferase, any of the prokaryotic DNA polymerases or DNA and RNA metabolic enzymes tested. TA and EA could prevent the growth of BALL-1 cancer cells, and the LD50 values were 11 and 48 microM, respectively. The cells were halted at G1 phase in the cell cycle. The mode of action of the triterpenoids against anti-inflammatory activity and their relationships to the DNA polymerase inhibitory activity and cell growth inhibition were discussed.

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