I Synthesis Of Cinchona Alkaloid Ligands II Synthesis Of Derivatives Of Gentiopicroside And The Antiviral Effects Of Them Against Coxsackievirus B3 And Simian Immunodeficiency Virus In Vitro

1 Synthesis of Cinchona Alkaloid LigandsSome disadvantages of conventional cinchona alkaloid ligand synthesis methods include high activities of acid-binding agent, rigorous reaction conditions, long reaction times, difficulties in preparation of the mono-cinchona alkaloid-derived ligands with high yield, use of toxic solvents, and significant amounts of waste product.In this study, we design and synthesize four kinds of different cinchona alkaloid ligands by the microwave irradiation method. The effects of irradiation power and temperature, irradiation time, catalysts and acid-binding agents on the yield are discussed in detail. The four kinds of cinchona alkaloid ligands were synthesized under the optimal mivrowave conditions with good yields in short reaction time and with no solvent pollution. The four kinds of cinchona alkaloid ligands were also synthesized using conventional methods. The difference between the conventional method and the microwave irradiation method is discussed. The results showed that under microwave irradiation, the reactions proceeded much faster and at a lower cost with higher yields of mono-cinchona alkaloid-derived ligands.2 Antiviral Effects of Gentiopicroside against Coxsackievirus B3 and its Mechanisms in VitroCoxsackievirus B3 (CVB3), a member of the Picornaviridae family that contains a single-stranded and positive-sense RNA genome, causes viral myocarditis (VMC) and can further develop into dilated cardiomyopathy in humans. Although the pathogenesis of CVB3 has been extensively studied in murine models and much work has been performed on the development of vaccines and therapeutic agents against CVB3, no virus-specific preventive or therapeutic procedures have been available to protect humans against enterovirus-induced heart muscle disease. In recent years, many countries are paying more and more attention to looking for anti-virus agents from Chinese medicinal herbs.Gentiopicroside (GPS), a secoiridoid glycoside isolated from traditional Chinese herbs, has various bioactivities, such as antibacterial, free radical scavenging and antiviral activities. However, little information is available in the literature about GPS's effects against CVB3 and the underlying mechanisms.(1) Synthesis of derivatives of GPSIn the present research, three derivatives of GPS were synthesized: derivative A, derivative B, and derivative C. (2) Antiviral effects of GPS and its derivativesWe determined the antiviral effects of GPS and its derivatives against CVB3 in vitro based on primary culture of myocardial cells of newborn SD rats. The results showed that GPS exhibited obvious antiviral effects in vitro. GPS inhibited pathologic change of cultured cardiac cells induced by CVB3. It also prevented the reproduction of CVB3 in myocardial cells and led to a significant decrease in activities of Aspartate transaminases (AST) and Lactic dehydrogenase (LDH) in myocardial cells compared with infected control groups. The antiviral effects of GPS were superior to those of the two derivatives.3 Antiviral Effects of Gentiopicroside and its Derivatives against SIV in vitroTo date, approximately 2 million people have died from AIDS, but there is still no safe, effective vaccine against the human immunodeficiency virus (HIV). Treatment of HIV-infected individuals with one or more drugs (AZT or DDC etc.) that interfere with the viral life cycle has provided a significant therapeutic benefit by reducing the clinical symptoms and prolonging the life of infected individuals. These therapies are not perfect, however, because they do not eradicate the virus, and treatment fatigue and/or the emergence of drug resistant strains eventually occurs which frequently heralds an increase in virus. So, the development of an effective drug is an urgent goal to control the global HIV epidemic. In the present study, we investigated the antiviral effect of GPS and its derivatives against simian immunodeficiency virus (SIV) in vitro. SIV and CEMx-174 cell system were employed as the models. The effects of GPS and compound A on antigen positive inhibitory rate, production of SIV virus, cytopathic effect and antigen positive inhibitory rate were studied. The viability of normal (control) and infected CEMx174 cells was determined by MTT assay. The results showed that compound A has a greater inhibitory effect on the activity of SIV in vitro when compared to GPS. Compounds B and C had no antiviral effects against SIV in vitro.