Studies On Synthesis And Bioactivity Of Novel Chalcones And Their Aminoalkyl-substituted Derivatives

Natural organic products of chalcones exist widely in glycyrrhiza or safflower medicinal plants,which are important intermediate in the synthesis of flavone.Chalcones derivatives show various biological activities because of their structure of basic 1,3-diphenylalkey ketone skeleton which makes them have great flexibility,can combined with different receptors.In recent years,scientists have carried out extensive and in-depth research and have made great progress,especially in the research and developments on antitumor、antiparasitic、anti-HIV、anti-flammation and ect biological activity.To find have favorable bioactivities agents,on the basis of synthesized-chalcone,novel chalcones derivatives have synthesized by combining bioactive moiety.The bioactive substructures of nitrogenous group we introduced in was via Hofmann N-Alkylation,of hydrogen we introduced in was via peroxide oxidation,throughout this way,we obtained containing potent pharmacological activity chalcones derivatives.1.2’-hydroxy-3,4,4’,6’-tetremethoxychalcone(1)was synthesized by Friedel-Crafts acetylization,O-methylation and Claisen-Schmidt condensation reaction with phloroglucinol as starting material.Eight novel aminoalkylated chalcone derivatives 2a-h were synthesized from 2’-hydroxy-3,4,4’,6’-tetramethoxychalcone(1)through extending alkoxy side chain at the 2’-position,and introducting amine hydrogen bond receptor at the end of the side chain.2.3,4,5-trimethoxybenzaldehyde reacted with peroxide MCPBA under alkaline conditions of sodium hydroxide to provide 3,4,5-trimethoxyphenol.Then the compound 2-hydroxy-4,5,6-trimethoxyacetophenone(3)was obtained from the Friedel-Crafts acetylization of 3,4,5-trimethoxyphenol.After that,the compound 3 reacted with substituted aromatic aldehyde under the catalisis of boric acid and formed a series of hydroxy-substituded chalcones derivatives 3a-d.Although the yields of the reaction is still not high,the products were easy to separated and purified.What’s more,the reaction provided a convenient methods to synthesis hydroxy-substituded chalcones successful in one step.3.2-Hydroxy-4,6-dimethoxyacetophenone reacted with potassium persulfate under alkaline conditions of pyridine and sodium hydroxide and formed 2,5-dihydroxy-4,6-dimethoxyacetophenone(4).Then the compound 4 reacted with substituded aromatic aldehyde under the catalisis of boric acid to provide a series of hydroxy-substituded chalcones 4a-4b.4.All of synthesized aminoalkyl-substituted polymethoxychalcone derivatives 1 and 2a-h were evaluated for antiproliferatives activities of three human cancer cell lines(Hela、HCC 1954 and SK-OV-3)by the CCK-8 assay,with cis-Platin and Paclitaxel employed as positive controls.The date of experimental showed that other chalcones nitrogen-containing derivatives showed moderate activity,except compounds 1 and 2e,especially compound 2c showed excellent IC50 on HCC1954 cell lines,and value of IC50 is 16.37μmol/L.5.The structure of all synthesized compounds have been confirmed by 1H NMR,13C NMR and MS.