Separation, Purification And Modification Of Anticancer Drug Ardipusillosideâ… and Preliminary Research Of Pharmacodynamics

Cancer is one of the most serious diseases that threaten humans. Every year, about 9 million people suffer from cancer, and 6 million people die from it. This equates to one person dying from cancer every second. Now, cancer has become the second greatest cause of death following cardiovascular disease. The anticancer drugs of chemotherapy have high side effects, toleration and so on. These shortages limit its use at clinic. Finding new drugs with good biological activity and low biotoxicity have become the first task for medical and chemical workers. In the clinical setting, a combination of some methods is always needed. Chinese traditional and herbal drugs have gained recent attention due to their special anticancer effects and their decreased side effects in comparison with traditional anticancer drugs. Finding new compounds with good biological activity and low biotoxicity through structural modification of naturally active components is an effective way to discover new anti-tumor drugs. ArdipusillosideⅠ(ADSⅠ) is a kind of new saponins with the original structure extracted and separated from Ardisia pusilla A. DC.. ADSⅠhas some certain antineoplasmic activities, it is not suitable for clinical application due to its low activity, large toxicity, and unsuitable injection administration. So this artic makes some Separation,purification, structural modification and reconstitution of ADSⅠas lead compound. And then, we research the anticancer activity of these compounds. Synthesis mainly includes the following three parts:First, extraction, separation and purification research on ADS I.As the content of ADS I is rarely about 1% in Ardisia pusilla A. DC., it is difficult to separated and purified. As a result we established a combinative method of traditional exaction technology and modern chromatographic fractionation according to technical research on its exaction and separation. It was exacted 4 times by ethanol (75%, v/v, 1000 mL) for 4 hours to obtain dry extractum at rate of 19.47%. HPLC condition:Chromatographic condition :Chromatographic column(10.0 mm×250 mm,sinochrom ODS-BP);Moving phase:CH3OH-H 2O(80:20);Flow rate:1.5 mL/min;Detect wavelength:205 nm。Its purity could reach 99%. Second, structural modification and structural modification of ADS I.1. use ADS I for lead compounds, and hydroxylamine hydrochloride and phenylamine hydrochlorate for raw material, Synthesize 2 similarity (A1,A2).2. design the synthesis of aglycon with ADS I. use this aglycon for lead compound, and hydroxylamine hydrochloride and phenylamine hydrochlorate for raw material, synthesize 2 similarity B1,B23. use A1 for raw material, react with Zn(II),Cu(II),Co(II),Cr(III),Ni(II), synthesize a series of metal-complexes C1-C54. use B2 for raw material, react with Zn(II),Cu(II),Co(II),Cr(III),Ni(II), synthesize a series of metal-complexes E1-E5Third, preliminary biological activity research.Cell tests on ADS I Schiff bases and their metal-complexes revealed that drug concentrations at 300μg/ml inhibited tumor cell proliferation significantly and had significant difference towards control group (P<0.01). Tumor control rate of E2 and E4 was obviously higher than that of crude drug.