8,9-methylenedioxybenzo[i]phenanthridines: topoisomerase I-targeting activity and cytotoxicity

Bioorg Med Chem. 2003 Aug 15;11(17):3795-805. doi: 10.1016/s0968-0896(03)00394-8.

Abstract

Substituted benzo[i]phenanthridines that have incorporated within their structure an 8,9-methylenedioxy group can exhibit topoisomerase I-targeting activity. Structure-activity studies were performed to examine the influence of saturation at the 11,12-positions of several substituted 8,9-methylenedioxybenzo[i]phenanthridines. The activities of these dihydro analogues were compared to those of their unsaturated analogues. In addition, the influence of varying substituents at the 2- and 3-positions within the A-ring of these 8,9-methylenedioxybenzo[i]phenanthridines on their relative potency as topoisomerase I-targeting agents and cell proliferation as determined using the MTT assay was investigated. 2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and its 11,12-dihydro derivative were among the more potent analogues evaluated with regard to topoisomerase I-targeting activity and cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division
  • DNA / metabolism
  • Humans
  • Phenanthridines / chemical synthesis
  • Phenanthridines / chemistry*
  • Phenanthridines / toxicity*
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*

Substances

  • Phenanthridines
  • Topoisomerase I Inhibitors
  • DNA