SYNTHESIS OF DROLOXIFENE CITRATE AND ITS NEW BIOACTIVITY

AIM　To investigate a feasible synthetic procedure of droloxifene and study on its new bioactivities. METHODS AND RESULTS　Droloxifene was synthesized using methoxybenzene and phenylacetic acid as starting materials, via Friedel-Crafts acylation, alkylation, demethylation, etherification, Grignard addition, elimination-dehydration, conversing configuration and forming citrate, totally 8 steps, overall yield 14.7% (9.2%^［1］). By pharmacological test, droloxifene citrate shows two new bioactivities: (1) obvious effect on reversing the MDR of K562/A02 cells and modulating mdrl, GSTπ and TopoIIα expression. (2) inducing apoptosis in cultured rat luteal cell. CONCLUSION　The improved synthetic procedure is shorter than the reported method by two steps and has advantages of simple separation, purification and conversion of configuration; easily available starting materials and reagents; concise operation. Two new bioactivities on reversing MDR and inducing apoptosis of luteal cell offered a clue in new drugs research and widened clinic application of droloxifene.