Synthesis And Anti-tumor Activity Of Polyamine Conjugates Based On 6-Substituted Benzo[cd]indol-2(1H)ones

Polyamines are a class of small organic molecules with many functions,which are composed of two or more amino groups and have bioactive aliphatic substances.In addition,polyamine conjugates can inhibit the metastasis of tumors.Recent years,the pharmacological activities of1,8-naphthaolactam derivatives have been studied.As DNA intercalators,polyamines have certain anti-tumor activities.Our group has been synthesized some 1,8-naphthaolactam-polyamine conjugates,in which compound TRG9 exhibits a strong antitumor effect,and a subcellular organelle is also identified as a lysosome.On the basis of previous studies in our group,two active sites in the structure were modified with 1,8-naphthalenelactam as raw material.Polyamines were introduced into active site 1.Aminomethyl,pyrazole,aminopyrimidine and benzimidazole rings substituted by aromatic rings were used to modify active site 2.Four series of 28,1,8-naphthaolactam-polyamine conjugates were obtained.Amine conjugates were confirmed by ¹H NMR,¹³C NMR,MS and elemental analysis.MTT assay was used to evaluate the antitumor activity of the synthesized target compounds in vitro.The antiproliferative activities of these compounds against various tumor cell lines?SMMC-7721,HepG2,HCT-116,Hela,CT-26,HT-29?and a normal hepatocyte HL-7702 were tested in vitro.The results showed that the target compounds CSD6 and CSD7 had higher inhibition rates on HCT-116,HepG2,Hela and SMMC-7721.Especially when the linked amine chain was non-natural triamine,they showed better biological activity than other derivatives.In terms of fluorescence properties,CSD6 exhibits stronger fluorescence intensity than TRG9.In the lung metastasis experiment of liver cancer in mice,compound CSD6 reduced lung metastasis rate as much as mitoxantrone,a control drug.