Nonhematotoxic naphthalene diimide modified by polyamine: synthesis and biological evaluation.

Abstract

With the aim of up-regulating antitumor efficacy and down-regulating adverse effects, three types of aromatic imide and diimides were designed to couple with different polyamines. The in vitro assays revealed that two naphthalene diimide-polyamine conjugates could inhibit the growth of multiple cancer cell lines more potently than amonafide. 9f, the most potent compound, was verified to efficiently induce apoptosis via a ROS mediated mitochondrial pathway in a preliminary mechanistic study. The comprehensive in vivo trials on three H22 tumor transplant models demonstrated that 9f improved the indexes in terms of inhibitive effect and lifespan extension and reduced the hematotoxicity which is one of main drawbacks of amonafide. More importantly, the obviously elevated ability in preventing lung cancer metastasis was observed, which increased the value of 9f as a promising lead compound. This work supported that the versatile function of polyamines may endow some intriguing biological features to the parent drugs.

• Authors: Yuxia Wang, Xingbo Zhang, Jin Zhao, Songqiang Xie, Chaojie Wang
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 55 Issue 7 Pg. 3502-12 (Apr 12 2012) ISSN: 1520-4804 [Electronic] United States
• PMID: 22428910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 American Chemical Society

Chemical References

• Antineoplastic Agents
• Imides
• Naphthalenes
• Polyamines

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Humans
• Imides (chemical synthesis, chemistry, pharmacology)
• Lung Neoplasms (drug therapy, secondary)
• Mice
• Naphthalenes (chemical synthesis, chemistry, pharmacology)
• Neoplasm Transplantation
• Polyamines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Transplantation, Heterologous