Synthesis And Biological Activity Of Naphthalene Diimides And Naphthalimides

Naphthalimide compounds,as a class of good DNA intercalating agent,have good anti-tumor activity and can be used as core skeleton of anti-tumor agents,anti-depressants,anti-protozoan agents and anti-viral agents.Amonafide is an inhibitor of DNA intercalator and topoisomerase II by inhibiting the binding of topoisomerase II with DNA,inducing apoptosis,and has been in the Phase III clinical trials.Polyamine including spermine,spermidine and putrescine etc,is a natural product of the human body.Besides,it is a multifunctional organic cation,which can promote the growth of some tissues.In this paper,on the basis of preliminary laboratory"naphthalimide-polyamine" we are trying to further expand the diversity of the target compounds and preliminary test their anti-tumor activity in vitro,the main research work is as follows:In the first part,two types of eighteen naphthalene diimides containing basic side chain were synthesized.At first,five symmetrical naphthalene diimides were designed and synthesized.Among three kinds of target compounds were synthesized by 1,4,5,8-naphthalentetracarboxylic dianhydride with three different polyamines were reacted and then 1,4,5,8-naphthalentetracarboxylic dianhydride and 3-brom-propylamine hydrobromide salt was reacted,following like to two kinds of basic side chains to give two target compounds.Secondly,thirteen asymmetric naphthalene diimides we designed and synthesized,Including ten naphthalene diimides which has n-butyl.side chain and three naphthalene diimides having hydroxypropyl side chain.In the second part,three types of seven naphthalimide compounds were synthesized.Firstly,Two kinds of naphthalimide compounds containing a carboxyl group were synthesized by Friedel-Crafts acylation,oxidation,substitution and other reactions using acenaphthene as material;Secondly,Three kinds of modified by polyamine of dual-substituted naphthalimide compounds were synthesized by nitration,substituted reactions and the 4-bromo-1,8-naphthalic anhydride was material;Finally two kinds of new amonafide derivatives were synthesized by the way of amonafide reacted with cinnamic acid and p-toluenesulfonic acid by acylation.In the third part,the antitumor activity of the target compounds in vitro of SMMC-7721,HepG-2 and colon cancer cell HCT-116 was tested,and we found that three naphthalene diimides containing hydroxypropyl groups C16,C17,C18 have better inhibitory activity on the above three kinds of tumor cells,and the interaction between C16 and DNA was also tested.