Design, Synthesis, And Anti-tumor Activities Of3,4-Diphenyl Coumarin Derivatives, And Their Interactions With Ct-DNA

Malignant tumor has become one of the major causes of death, the treatment of which has been a worldwide problem. Currently, chemotherapy is still the main treating method on clinical trial. Many antitumor drugs have been successfully used in the clinical trial. However, with the continuously enhance of the drug resistance to tumor cells, existing drugs cannot meet the needs of cancer patients. Therefore, it has been one of the important research topics to look for effective anti-cancer drugs in the medical community of the world.In this paper, based on the advantages of the coumarins as antitumor agents which targets on DNA, and as the continuations of our research on the coumarins, we designed and synthesized a series of3,4-diarylcoumarins5a-d and9a-d with two amino side chains on different positions. Their structures were identified by NMR and MS spectra, and the antitumor activities of the target compounds has been evaluated. Some of showed good anti tumor activities. Structure activity relationships (SARs) analysis suggested that the distance between the side chains and the amino alkyl chain would play an important role in the compounds against tumor cells proliferation. The binding properties of Ct-DNA and compounds5b、5e、5f、9b、9e and9f were evaluated by UV-vis, fluorescence, circular dichroism spectras and DNA melting temperature test. The results showed that these compounds could mainly acted in a intercalative binding mode with Ct-DNA.