Development of novel bis-naphthalimide derivatives and their anticancer properties

Abstract

A series of novel N,N-bis(3-aminopropyl)methylamine-bridged bis-naphthalimide derivatives NI1–6 were designed and synthesized. Their cytotoxic activities against Hela, MCF-7, SGC-7901 and A549 cells were investigated. Compounds NI1–6 exhibited selectively cytotoxic activities in the tested cell lines and lower cytotoxic activities against MCF-7 cells were found except for compound NI1. NI1, the N-(2-hydroxyethyl)piperazine-modified naphthalimide, showed potent cytotoxic activity in the tested cell lines with IC₅₀ values of 2.31, 2.94, 0.88 and 1.21 μM, respectively, better than the control drug (amonafide). Furthermore, its DNA binding properties, fluorescence imaging and collective apoptosis were investigated. Interestingly, NI1 as a DNA intercalator showed fluorescence enhancement upon binding with Ct-DNA and exhibited different impacts on the cell cycle compared with amonafide. Moreover, compound NI1 showed no significant hematoxicity and cardiotoxicity.