Poria cocos 균핵에서 분리한 성분들과 DNA Topoisomerase I의 반응양상 및 효소저해 활성

Binding Mode and Inhibitory Activity of Constituents Isolated from Sclerotium of Poria cocos with DNA Topoisomerase I

DNA topoisomerase I (TOP1) helps the control of DNA replication, transcription and recombination by assisting breaking and rejoining of DNA double strand. Camptothecin (CPT) and its derivative, topotecan, are known to inhibit TOP1 by intercalating into TOP1-DNA complex. Recently various non-CPT intercalators are synthesized for a new class of TOP1 inhibitors. In this study, six compounds isolated from Poria cocos were investigated for their interaction with TOP1-DNA complex using the flexible docking program, FlexiDock. The binding modes were analyzed and compared with the TOP1 inhibition activities. The compounds that showed potent activity were intercalated between the +1/-1 base pairs of DNA, located near the active site phosphotyrosine723 and formed hydrogen bonds with active site residues. On the other hand, compounds with no activity were not docked at all. The binding modes were well correlated with the inhibition activity, suggesting the possibility that potent inhibitors can be designed from the information presented by the docking study.