A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor.

ABSTRACT: The biological activity of indenoisoquinoline topoisomerase I inhibitors is significantly enhanced by nitration of the isoquinoline ring. In the present study, nitrated analogues were synthesized with the indenone ring substituted with methoxy groups to further explore a previously identified structure-activity relationship between the nitrated isoquinoline ring and a methylenedioxy-substituted indenone ring. The results indicate that a single methoxy group at the 9-position of an indenoisoquinoline affords superior biological activity. Hypothetical binding models have been developed to rationalize these results, and they indicate that pi-stacking between the indenoisoquinolines and the DNA base pairs, as visualized by electrostatic complementarity, is important for the intercalation and b

SUBMITTER: Morrell A 

PROVIDER: S-EPMC2526352 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature