Structure-Based Design, Synthesis, and Biological Studies of New Anticancer Norindenoisoquinoline Topoisomerase I Inhibitors
Citations Over TimeTop 17% of 2010 papers
Abstract
On the basis of the superimposition of the crystal structures of norindenoisoquinoline 5 and topotecan (2) bound in the topoisomerase I-DNA covalent complex, as well as molecular docking and quantum chemical calculations, the substituted norindenoisoquinoline 14a was designed by transporting the 9-dimethylaminomethyl group of topotecan to the 10-position of the norindenoisoquinoline 5. The desired compound 14a was synthesized and found to possess topoisomerase I inhibitory activity that was slightly better than that of the starting compound 5. A focused set of 10-substitued norindenoisoquinoline analogues were then synthesized. The imidazole-substituted compound 14c was highly cytotoxic when evaluated in a series of human leukemia, ovarian, and breast cancer cells.
Related Papers
- → DNA-Topoisomerase I, a new target for the treatment of neuroblastoma(1997)47 cited
- → Glioma cell sensitivity to topotecan: the role of p53 and topotecan-induced DNA damage(2001)29 cited
- → Topoisomerase I interactive drugs in children with cancer(1996)49 cited
- Intermittent exposure of medulloblastoma cells to topotecan produces growth inhibition equivalent to continuous exposure.(1997)
- Topotecan: what dose, what schedule, what route?(1999)