Synthesis Of Isoandrographolide Derivatives

AIDS is the abbreviation of Acquired Immunodeficiency Syndrome (AIDS). This disease is caused by HIV infection, CD4+cells decrease, and damage of immune function, which can lead to a variety of microbial infection or tumor. And it is characterized by a high mortality rate of infectious disease. AIDS treatment easily leads to virus resistance, and with the dose increasing, patients can not suffer from the tolerance and the high cost of drugs.Meanwhile, the incidence of cancer has shown a growing tendency, and this disease has already become a major threat to human life. According to an investigation, cancer causes about6.3million deaths every year, and by2020this figure may double. Therefore prevention and treatment of cancer is still a major challenge in21st century.Traditional Chinese medicines and natural products have a wide range of biologically active substances, to which more and more attentions have been attracted in order to find low toxicity, low side effects, and unique function of anti-AIDS and anti-tumor drugs or drug-assistants.Andrographolide, the main bioactive component of Andrographis paniculata, is diterpene esters obtained form Acanthaceae Andrographis plant, and has the detoxifying and anti-inflammatory activities. Andrographis extract combinated with Zidovudine (AZT), can enhance the anti-HIV activity of the later through synergy effect. Dehydrandrographolide succinate monoester (DASM) inhibits HIV-1inducing cell cycle disorders, and increase CD4+lymphocyte levels of HIV-1infected patients. The mechanism is similar to that of the first generation of anti-HIV drug zidovudine. In vitro study, the Andrographis Paniculta lactone shows antitumor activity against breast cancer MCF-7cell, esophagus cancer tumor cells, Ec9706cell, colon cancer HCT-8, HCT-116cell, and prostate gland cancer PC-3.The α, β-unsaturated-y-lactone structure of Andrographolide is the active group, which is the common structure for lots of natural products with anti-viral activity. Andrographolide structure itself is labile and its isomerization product Isoandrographolide(IA) can enhance the stability, with the α, β-unsaturated-γ-lactone pharmacodynamics structure remained, which is a ideal lead compound for further structural modification. In the present study, with Isoandrographolide as the lead compound,17Isoandrographolide esters derivatives named from S-1to S-17were designed and synthesized and4glucoside derivatives named from T-1to T-4. With the biological activity research, the derivative with improved activity and stability are expect to be obtained, for the foundation for further anti-AIDS and anti-tumor study.