The Synthesis Of Dehydroandrographolide Cyclophosphate Derivatives And Their Antitumor Activities

Andrographolide, molecular formula C20H30O5,which is diterpene lactones extracted in Acanthaceae Andrographis, shows many activites such as anti-inflammatory and anti-viral effect, anti-tumor, immune regulation, protective and choleretic treatment of cardiovascular and cerebrovascular diseases, anti-diabetic anti-fertility. Pharmacological study of the andrographolide its derivatives in past laid particular emphasis on anti-viral anti-bacterial and anti-inflammatory activities, while in recent years, further research of their activities of anti-tumor and immune regulation has made headway, especially anti-tumor effect.Organic phosphorus compounds are extremely important substance in life process. There are a lot of organic phosphorus compounds in nature and organisms, and in the living body many endogenous active substances containing a organic phosphate structural unit which bear a part in almost all life process such as energy transformation, metabolism, genetic expression and so on. In past study, Organophosphorus drugs as antineoplastic has been made important discoveries and used in clinical, such as broad-spectrum anti-tumor Cyclophosphamide, Ifosfamide, Gan phosphoryl nitrogen mustard, Atenolol the piperazine, iodine behalf piperazine, Thiotepa, The chlorine phosphoramides, phosphine Helo Plymouth. Thereamong because of toxic side effect of cyclophosphamide, it has been replaced by other anti-tumor. However, the research of new anti-tumor has never ceased.According to literature, most andrographolide derivatives have good biological activity. Because of lactone ringits and 1,3-diol in their structure, they can inhibit growth of tumor and have the ability of anti-HIV. In this article, andrographolide is used as lead compound, and by its structural modification, we designed and synthesize a series of andrographolide cyclic phosphate derivatives. By adding cyclic phosphate and cyclophosphamide to 3-,9-of andrographolide,it is propitious to improve drug lipid solubility, thus expected to enhance the selectivity of the drug reducing its toxicity.In addition,the new structure of the compound is analyzed and concained by IR,MS and 1H-NMR. Furthermore, antitumor activity in vitro experiments of these new compound are made, and the result show that the synthesized andrographolide cyclic phosphate derivative has a good inhibitory activity of the tongue cancer TCA-8113 cells in vitro.