Synthesis And Biological Activities Of Triazol-Naphthalimides

Several series of 1,2,3-triazoles containing heterocyclic and naphthalimides compounds were designed and synthesized and their spectra properties,DNA intercalative,antitumor and DNA photo-damaging activities were evaluated.A series of 1,2,3-triazoles fused 1,8-naphthalimide derivatives with electron-deficiency characteristics were designed and synthesized.Their spectra properties,DNA intercalative, DNA photo-damaging and antitumor activities were evaluated.The scatchard binding constant between CT DNA with K1 was monitored by fluorescence spectroscopy technique. The result showed that K1 could effectively intercalate into the CT DNA and the scatchard binding constant reached 10⁵ M^-1.Titration CD spectra of CT DNA by K2 illustrated that the mode of K2 interacted with DNA changed from intercalation to aggregation with the concentration of K2 increased.It also revealed that the CT DNA unwound upon K2 intercalation,followed by which the tertiary structure of CT DNA underwent a transition from B-form to A-like conformation.DNA photo-damaging assay showed that these compounds could effectively cleave supercoiled DNA.The antitumor activities test of these compounds exhibited efficient activities against U251,A549 and MOLT-4 cell lines.A series of 6-1,2,3-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 CT DNA by V2 illustrated that the mode of V2 interacted with DNA changed from intercalation to aggregation with the concentration of V2 increased.It also revealed that the CT DNA unwound upon V2 intercalation,followed by which the tertiary structure of CT DNA underwent a transition from B-form to A-like conformation.DNA photo-damaging assay showed that these compounds could effectively cleave supercoiled DNA.The inhibitory test against A549 and MOLT-4 cell lines in vitro of V2 showed that this compound exhibited high antitumor activities,IC₅₀ of compound V2 against A549 cell reached 0.426μM.A series of 5-1,2,3-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.The scatchard binding constant between CT DNA with F1 was monitored by fluorescence spectroscopy technique.The result showed that F1 could effectively intercalate into the calf thymus DNA and the scatchard binding constant reached 10⁵ M^-1.DNA photo-damaging assay showed that these compounds could effectively cleave supercoiled DNA.The inhibitory test against A549 and MOLT-4 cell lines in vitro of I2 and F2 showed that the compounds exhibited high antitumor activities,especially IC₅₀ of compound F2 against A549 cell reached 0.333μM.These two compound also exhibited high selectivity against A549 and MOLT-4 cell lines.