Synthesis And Bioactivity Study Of Novel Naphthyl Nitro-heterocyclic Compounds

Based on series of triazoles containing heterocyclic and naphthalimides compounds were designed and synthesized and confirmed by NMRJR and HRMS. Their spectra properties, DNA intercalative, antitumor and DNA photo-damaging activities were evaluated.Novel2,1,3-thiadiazole fused1,8-naphthalimide derivatives had been synthesized and the results of UV-Vis spectra, Fluorescence spectra, CD spectra and viscosity measurement all showed that the compounds had good DNA binding ability.2,1,3-thiadiazole fused1,8-naphthalimide derivatives S1binding constant could reach2.83×105mol-1·L. The change appeared in the CD spectra of DNA when incubated with2,1,3-thiadiazole fused1,8-naphthalimide derivatives S1and2,1,3-thiadiazole fused1,8-naphthalimide derivatives S4illustrated that the compounds interacted with DNA by the classical intercalating mode, making the positive band increase and the negative band decrease. All the2,1,3-thiadiazole fused1,8-naphthalimide derivatives compounds could cleave supercoiled plasmid DNA, especially S3. S1-4,,bearing flexible amine side chains, showed excellent cytotoxicity to the selected MCF-7,7721, Hela, A549and HL60cell lines.The derivatives of Benzo[c, d]indol-2(H)-one have been synthesized. Their DNA bonding properties were evaluated through UV-Vis spectra, Fluorescence spectra and CD spectra combined with viscosity measurement. The result showed that compounds can efficiently intercalate base pairs of CT DNA, while AC3’s bonding constant is Kb=1.65×105mol-1·L. DNA photo-damaging assay were taken with pBR322plasmid. All the compounds are efficient to cleave super-coiled DNA, while AC1-6can photo-cleave super-coiled DNA into linear fragments. AC6showed that this compound exhibited high antitumor activities, IC50of compound against MCF-7cell reached3nM.Two series of triazol-1,8-naphthalimide derivatives were designed and synthesized via "Click Chemistry". Their spectra properties, DNA intercalative, DNA photo-damaging and antitumor activities were evaluated. Titration CD spectra of DNA by compounds illustrated that the mode of compounds interacted with DNA changed from intercalation to aggregation with the concentration increased. In particular, compound bearing N,N-dimethylethylenediamine with the values of IC50against three cell lines was5.6-fold,2.4-fold,and8.5-fold lower than that of Amonafide, and other compounds bearing aminoalkyl side chains were all more potent than Amonafide. DNA photo-damaging assay showed that these compounds could effectively cleave supercoiled DNA. The compounds were more toxic against7721than MCF-7and Hela cells.