5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h]naphthyridin-6-ones and related compounds as TOP1-Targeting agents: influence of structure on the ternary cleavable complex formation

✍ Scribed by John E. Kerrigan; Daniel S. Pilch; Alexander L. Ruchelman; Nai Zhou; Angela Liu; Leroy Liu; Edmond J. LaVoie

• Book ID: 104364096
• Publisher: Elsevier Science
• Year: 2003
• Tongue: English
• Weight: 318 KB
• Volume: 13
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(03)00797-2

✦ Synopsis

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.