Study On Synthesis And Biological Activities Of Containing Heterocyclic Dihydroartemisinin Derivatives

Artemisinin, also known as "yellow arteminisinin", is a good antimalarial sesquiterpene lactone compound, which first extracted by Chinese chemist from Artemisinin annua in1972, and is the first-line drug of antimalarial. Modern pharmacological studies confirmed that artemisinin and its derivatives, has anti-parasitic, anti-pregnancy and anti-tumor immune function and many pharmacological effects, except from antimalarial. However, the researchers found that Plasmodium have had potential resistance of this class of drugs, thus it is very important and urgent to discover and develop the new antimalarial drugs. Therefore, synthesis the new anti-malarial drugs, the anti-cancer drugs, and which research and development will be a very meaningful thing. Dihydroartemisinin is important derivative in vivo metabolites of artemisinin, because it has better and higher activity than artemisinin. These years, many researches have been made in the structural modification and pharmacological activity researches, and have made a lot of productive work. However, the reports about the synthesis of containing heterocyclic and glycosylation dihydroartemisinin derivatives and biological activities is rare, and structure-activity studies on heterocyclic drug is still a most dynamic research area. Whereas the unique role of the amide bond and glycosidic bond in organisms, in order to develop new drug candidates or lead compounds with low toxicity, high activity, stabilization and controllable quality, we used sub-structure splicing activity modification methods with biological activity tests which based on the analysis of the matrix structure of dihydroartemisinin and research on the chemical reaction of its several functional groups, to carry out the structural optimization research. The main contents of this paper have the following two aspects:1> Synthesis of containing novel heterocycle dihydroartemisinin derivatives. In this study, we have designed and synthesized three series including28dihydroartemisinin derivatives by chemical methods, which are:(1) Dihydroartemisinin-10-siperazine-sulfonamide derivatives;(2) Dihydr oartemisinin-10-siperazine-amide derivatives;(3) Dihydroartemisinin-10-siperazine-glycosylation derivatives;(4) Try the reaction research of dihydroartemisinin piperazine and furan Ketones. They have not been reported in the literature or patent. All these compounds are identified by IR,1H NMR,13C NMR, HRMS.2、Biological activity of heterocyclic dihydroartemisinin derivatives. We selected some representative compounds, and examined their biological activity of in vitro anticancer. The result shows that target compounds have the inhibitory activity on in vitro cultured human cervical cancer Hela cells. The preliminary bioassay test shows that compound5c showed the best inhibition activities against Hela with1C5O0.14uM. This result indicates these compounds could inhibit the cancer cell proliferation, and induce apoptosis.It is very important for screening of new anti-cancer and antimalarial drugs.