Synthesis And Biological Evaluation Of DNA-targeted Anticancer Heterocycle-fused Naphthalene Compounds

Designed, synthesized three series of compounds by modifying classical matrix naphthalimide and acenaphtho-heterocycle.Their structures were proved by MS and1HNMR. We used UV-vis spectra, Fluroresence spectra viscosity assay and CD spectra to observe their DNA binding abilities. To futher evaluate their biology activity, we employed MTT assay to learn their cytotoxicity.Successfully designed and synthesized a novel naphthalimide derivatives containing2-4(aminophenyl)benzothiazole. These compounds could intercate into DNA base pairs, which was proved by UV-vis spetra, Flurorensence spectra, viscosity and CD spectra. They could also turn the conformation of DNA from B to A-like.All of the compounds showed improved cytotoxicity against MCF-7, Hela and7721cell lines. The IC50values were between4-5μM.Acenaphthequinone was used as starting material, after being bromination and other reactions, we finally got a series of acenaphthp[1,2-b]quinoxaline derivatives.All compounds were verified by TOF MS and1HNMR.Except E2,all compounds interacted with DNA by intercalating.All compounds exhibited excellent inhibition of growth of cancer cell lines,in particular E3,the IC50value against MCF-7was1.99μM.By linking different heterocycle to acenaphthequinone, we designed and synthezied a series of compounds.After interacting with DNA, all compounds’ flurorensence enhanced, in particular F3,which increased1.2times.CD spectra of F1suggested it could stabilize the B-DNA,while CD spectra of F2and F3implied that they could change the B-DNA to C-DNA.From MTT assay,we learnt that F2and F3were more cytotoxicity than Fl.