11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents

  • Bioorg Med Chem. 2008 Sep 15;16(18):8598-606. doi: 10.1016/j.bmc.2008.08.018.
Wei Feng  1 ,  Mavurapu Satyanarayana ,  Yuan-Chin Tsai ,  Angela A Liu ,  Leroy F Liu ,  Edmond J LaVoie
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
PMID: 18771930 DOI: 10.1016/j.bmc.2008.08.018
Abstract

Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC(50) values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402.