Synthesis And B Iological Evaluation Of DNA-targeted Anticancer Drugs Of Naphthalimide Derivatives

According to the molecular hybridization principles,three series of 16 novel DN Atargeted anticancer drugs were synthesized by choosing naphthalimide and coumarin as DNA intercalators and cyanuric chloride derivatives and cholesterol as the pharmacophores.Their structures were identified.Inhibitory activity of cancer cells in vitro and the interaction mode between the compounds and DNA were evaluated.8 novel coumarin instead of naphthalimide derivatives had been synthesized by esterification or amidation reaction with an alcohol amine and a diamine as a bridge.The structures were identified by HRMS,13 CNMR,1HNMR.The inhibitory activity of cancer cells in vitro showed that the compounds had excellent inhibition activity against A549 cells.In particular,N8 exhibited the best inhibitory abilities against A549 cells(IC50,5.18 μM)and the best selectivity.The UV-vis spectra,Fluroresence spectra,CD spectra and viscosity assay showed that the compounds could intercalate into DNA.4 novel naphthalene derivatives as DNA-targeted Anti-cancer drugs had been synthesized by introducing the decorated cyanuric chloride derivatives into 4-bromine-1,8-naphthalene anhydride with aminocaphenylazine as a bridge.The structures were identifyied by HRMS and NMR.The inhibitory activity of cancer cells in vitro showed that all of them had improved inhibition activity in micro molarity.Compound S3,a potential drug for the treatment of breast cancer,exhibited good inhibitory abilities against MCF-7 cells(IC50,20.56 μM).Compound S4 exhibited the best inhibitory abilities against Hep G2,MCF-7,A549 cells(IC50,18.21,16.78,17.85 ?Μ,respectively).The UV-vis,fluroresence,CD spectra and viscosity assay showed that the compounds could intercalate into DNA.4 cholesterol derivatives as DNA-targeted Anti-cancer drugs had been synthesized by introducing cholesterol into naphthalimide and coumarin,respectively.The structures were identified by HRMS,13 CNMR,1HNMR.The inhibitory activity of cancer cells in vitro showed that compound D1,D2 were better than compound D3,D4 and reached the highest inhibitory activity against MCF-7 cells(IC50,18.44 and 17.58 ?Μ,respectively).Compound D1 had the best selectivity whose IC50 value against RAW246.7,Hep G2,Hela,A549 were 2,1.7,1.9,1.4 fold higher than MCF-7.The UV-vis spectra,Fluroresence spectra,CD spectra and viscosity assay showed that the compounds could intercalate into DNA.