Naphthalimide intercalators with chiral amino side chains: effects of chirality on DNA binding, photodamage and antitumor cytotoxicity.

Abstract

Several novel heterocyclic-fused naphthalimides intercalators with chiral amino side chains were investigated. Their side chains' chiral configuration determines DNA binding activities in the order: S-enantiomers > R-enantiomers. And their DNA photodamaging activities were in good agreement with their DNA binding constants, the S-enantiomers could photocleave circular supercoiled pBR322 DNA more efficiently than their R-enantiomers. S-enantiomer B(3) could photodamage DNA at 0.2 microM and cleave supercoiled plasmid DNA from form I to form II completely at 50 microM. Almost all of these intercalators showed effective cytoxicities against human lung cancer cells and murine leukemia cells. S-enantiomers showed different antitumor cytotoxicity by comparison with R-enantiomers. This work may provide additional information for the role of amino side chains on intercalators as antitumor agents.

• Authors: Qing Yang, Peng Yang, Xuhong Qian, Lianpeng Tong
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 23 Pg. 6210-3 (Dec 01 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18930399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Intercalating Agents
• Naphthalimides
• DNA

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• DNA (chemistry, drug effects)
• Drug Screening Assays, Antitumor
• Humans
• Intercalating Agents (pharmacology)
• Mice
• Molecular Structure
• Naphthalimides (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism
• Structure-Activity Relationship