5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones and related compounds as TOP1-targeting agents: influence of structure on the ternary cleavable complex formation.
In this paper, we present our results from a docking study of the title compounds with the DNA/topoisomerase I complex based on the recently published X-ray crystal structure of the topotecan/DNA/topoisomerase I ternary cleavable complex (Staker, B.L., et al. PNAS 2002, 99, 15387) using the Autodock program. Simple intermolecular docking energies (E(dock)) correlate well with in vitro DNA cleavage data suggesting that the binding mode from the crystal structure is a reasonable binding mode for these compounds.
D018360:Crystallography, X-Ray; D004264:DNA Topoisomerases, Type I / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry* / Q000494:pharmacology
D009287:Naphthyridines; D004264:DNA Topoisomerases, Type I