Synthesis And Antitumor Acitivity Of Novel Isoliquiritigenin Analogues

Isoliquritigenin is one of the most important chalcone compounds from licorice, it has a variety of biological activities. Antitumor effect is the research focus in recent years. In recent years, active principles from plant are used as lead compounds to design and develop new drugs, it is an important channel for searching new drugs. On the foundation of references, This thesis used 4-hydroxybenzaladehyde and 2,4-dihydroxyacetophenone as initial substrate, isoliquritigenin has been optimized and synthesized. Isoliquritigenin is as lead compound, on the foundation of computer-aided design, full consideration of structure characteristics of isoliquritigenin and leave intrinsic active hydroxyl groups, the structure of isoliquritigenin is modified through Mannich reaction, 10 isoliquritigenin derivatives on 3' aminomethyl substituted have been designed and synthesized. The structures of these compounds are identified by NMR(¹H, ¹³C),MS,IR,UV. Synthetic derivatives are obtained by introduct of a aminomethyl group into isoliquritigenin, water-solubility of isoliquritigenin and its bioavailability has been improved.In the process of isoliquritigenin synthesis, the yield and purity of pivotal procedure aldol condensation reaction are considerably affected by mole ratio of aldehyde and ketone and reaction time. We have derived optimum conditions of aldol condensation reaction through optimization: M (aldehyde): M (ketone) =1.8: 1, barium hydroxide as catalyst, reaction temperature 45℃, reaction time 12 h. On these conditions that yield of isoliquritigenin is 77.9%.In the process of isoliquritigenin derivatives synthesis,the mole ratio of isoliquritigenin: formaldehyde: amine is 1: 1.2: 1.2, glacial acetic acid is both catalyzer and reaction solvent. Preparation procedure of this reaction is simple , conditions are bland, the products are easily purified. The yield 25%-42.8%.Antitumor activities in vitro of 10 derivatives toward human prostatic cell line PC-3, human mammary cancer cell line MCF-7, human oophoroma cell line HO-4980 IC50 are all more than isoliquritigenin. But tumor control rate in vivo of compound 3'-diisopropyl-aminemethyl-2',4,4'-tryhydroxychalcone (71.68%) is obviously superior to isoliquritigenin. The foundation of scientific research is offered for isoliquritigenin new drugs.