Design And Synthesis Of3,4-diphenyl Coumarin Trimer Derivatives, And Their Interactions With Ct-DNA

Coumarin is an important kind of natural products which is widespread in secondarymetabolites of higher plants with a structure of α-BenzoPyranone. Its biological activitiesincludes anti-tumor, anti-oxidation, anti-HIV, anti-bacterial, anti-osteoporosis, and thuscoumarin has been extensively researched and has drawn widely attention. In recent years,reported new coumarin derivatives are mainly hybrid coumarin, coumarin with a fusedheterocyclic structure and oligomeric coumarin. Based on the principle of hybrid in drugdesign, we synthesised series of coumarin-tristyryl hybrid derivatives3,4-diarylcoumarinmonomers with flexible side chains and they gave a good anti-tumor activity. In this paper, weprepared its trimer derivatives8and9with trimesic acid as a linker. All their structures wereidentified by NMR and MS spectra. The binding properties of Ct-DNA and compounds7a、7d、8a、8d、9a and9d were evaluated by UV-vis, fluorescence, circular dichroism spectras andDNA melting temperature test. We tested the fluorescence lifetime of compounds8a,9abefore and after their intercalation with DNA. Studies have shown that trimeric compound9a,9d would appear obvious hyperchromic effect of UV, fluorescence intensity increases, thefluorescence lifetime growth and increasing of DNA melting temperature respectively afterthe interaction with DNA. Their binding constants with DNA were greater than8a,8d, butlower then their monomer7a,7d. The results showed that these compounds could mainlyacted in a intercalative binding mode with Ct-DNA. We initially tested the in vitro anti-tumoractivity of compounds8a and8d with human cervical cancer Hela cells and human breastcancer MCF-7cells. The result showed that compound8a has a medium Hela cellproliferation inhibition activity, stronger than8d, indicating that a different side chain ofamino has a impact on the anti-tumor activity of compounds.