Synthesis Of Di-curcumin Aminophosphate Esters And Study On Its Preliminary Pharmacokinetic Properties

Mustard is a kind of alkylating agents，which is lethal to tumor cells and has beenapplied in clinical. However, the drug has low therapeutic index and poor targeting. Itis expected to be improved by chemical structural transformation.Curcumin with safety and good tolerance, has a broad spectrum of pharma-cological activity. However, its poor aqueous solubility, instability of chemicalstructure and low blood concentration are the main causes of low bioavailability,which hinders the clinical application of curcumin. To be comfortable, prodrug modi-fication is an effective method to improve curcumin’s pharmacokinetic properties.In this paper, according to the metabolic pathways and the anti-tumor mechanismof cyclophosphamide, three kinds of di-curcumin aminophosphate esters are designedand synthesised under the guidance of prodrug design and association principle. Theproducts are analyzed by LC-MS, GC-MS,1H NMR and IR. All of the products arelipophilic and have a better stability in PH=7.4of phosphate buffer solution and blood.More important, the products are able to release curcumin in vivo. Assay theanti-tumor activity of products by MTT method. The results show that all of productsdo not inhibit the growth of cervical cancer cells in vitro. This is consists with thetheoretical analysis and requires further study in vivo.