Betulinic acid and its derivatives, potent DNA topoisomerase II inhibitors, from the bark of Bischofia javanica.

DNA Topoisomerases (Topos) II are target enzymes for anticancer chemotherapeutic drug development. Bioassay-guided fractionation of the CHCl3 extract of the bark of Bischofia javanica led to the isolation of betulinic acid (1) and its derivatives, betulonic acid (2), 3beta-O-(Z)-coumaroylbetulinic acid (3), and 3beta-O-(E)-coumaroylbetulinic acid (4). These compounds were found to be catalytic inhibitors of Topo II activities with IC50 values ranging from 0.38 to 58 microM. The acylation of the OH group at C(3) of betulinic acid exhibited stronger Topo II inhibitory activity.