Naphthalimides Modified By Polyamine:Design, Synthesis And Antitumor Activity Evaluation

In recent years polyamine conjugates modified by polyamine in terms of anti-cancer agents has aroused widespread concern, the study showed that natural or synthetic polyamines have the potential to develop into an effective use of the cell membrane polyamine transporter (PAT) of the targeting vector, which may have improved selectivity and capacity of the cells of biologically active compounds.Naphthalimide derivates as anticancer drug research, we have found that some of the classic compounds such as amonafide (amonafide) and mitonafide (mitonafide), which amonafide already in Phase Ⅲ clinical trials. In clinical trials, scientists found some of its shortcomings, such as neurotoxicity, bone marrow suppression and travel to the opposite sex, such as the performance of different tumorsIt was found that a large number of naphthalimide antitumor compounds, showed strong inhibition, while the inhibition of tumor metastasis and has a good effect.Naphthalimide derivatives for the purpose of efficiency and structural modifications to reduce toxicity and other adverse reaction, increased targeting of these compounds on tumor cells. This article, based on polyamine serveing as efficient vectors to carry drugs and increaseing the selectivity of drug departure, is mainly to complete the following tasks:(1) Describes the current significance of polyamines and derivatives naphthalimide pharmaceutically has new developments and recent research.(2) By modifying the amino of amonafide and4-bromine1,8naphthalene dicarboxylic anhydride, two series of linear polyamine conjugates derivatives were designed and synthesized. At the same time, through the "arm" anti-pharmacological changing in the structure, their antitumor activities were tested so that the interesting anticancer leads were obtained.Two series of11target compounds by synthesized, include nine propionylation naphthalimide derivatives and two ’arm’ polyamine conjugates. Their structures were confirmed by1HNMR, MS and elemental analysis. Their antitumor activities were also bioevaluated by MTT assay on HepG2(liver cancer cells) inhibition. The results showed that some of the drugs target compounds in vitro antitumor activity was significantly better than amonafide which has been in phase Ⅲ clinical trials, and wherein the compounds7c,7d,7e,11i,11j displayed good antitumor activities.