Synthesis And Bioassaies Of Artemisinin Derivatives&Research Of Quality Standard And Stress Testing Of Potential Schistosomicide

Artemisinin, an unusual sesquiterpene bearing lactone and endoperoxide linkage, was an important lead compound for drug design. Derivatives of artemisinin have been used as antimalarial agents in clinical treatment for many years with great therapeutic efficacy, toleration and low toxicity. Artemisinin-like compounds have been known to be effective against a range of diseases with antitumor activity, antischitosomal activity and antiviral activity. Introduction of additional heteroatoms to the skeleton of artemisinin will afford derivatives with novel biological properties, and studies on the synthesis method of amino derivatives are the topic and focus of scholars. Furthermore, piperazine, a good synergistic group has diverse biological activities such as antitumor, antimalaria, antibacterial etc.Based on the background, we introduced four representative piperazine-like compounds to C-10position of artemisinin to develop more potent antitumor and antischitosomal agents by four-step synthesis. First, artemisinin was reduced to compound2with a yield of89%by NaBH4in methanol at0-5℃. Then, compound3was synthesized in a yield of94%with the molar ratio of compound2: trimethylchlorosilane:triethylamine=1:1.2:2in anhydrous dichloromethane at0-5℃. Further, compound3was converted to compound4with a molar ratio of1:1.02with trimethylsilyl bromide in anhydrous dichloromethane at0℃, the reaction solution could be used in next step without purification. Finally, to the solution of four representative amines were added the above solution at0℃· to obtain four novel and representative artemisinin derivatives5a-5d. The structures of the new derivatives of this study were identified by1H-NMR,13C-NMR and HR-MS. The antitumor activities of the derivatives were evaluated by MTT assay against SH-SY5Y, MCF-7and HepG2cell lines.5b,5c and5d exhibited inhibitory activities against the three cell lines while5a showed antitumor activity against SH-SY5Y and HepG2cell lines. The findings provide the theoretical and experimental value for the development of anticancer drugs. The antischistosomiasis activity of the derivatives also were being tested. The study will provide new insights that will hope fully lead to the development of more effective treatment options for a variety of diseasesIn addition, in order to ensure the safety and efficacy of candidate schistosomicide, to know its original stability, explore the affecting factors of the stability and its possible degradation products, study the preparation process, packaging and storage conditions of the compound, the paper studied the quality standards and stress tests of potential schistosomicide. Quality standards were studied in terms of physical traits, identification and assaying, and stress tests, including high temperature test, humidity test and strong light test, were carried out. The result showed the appearance of compound had no obvious chang in60±1℃, RH(75±5%), but its content decreased. It should be preserved in a dry and cool place. The appearance and content of the compound had no obvious chang in the environmental illumination of4500±500Lx. The preservation of the compound does not need to avoid light.