Related Experiment Videos
[Synthesis of droloxifene citrate and its new bioactivity]
1Department of Organic Chemistry, School of Pharmacy, Shanghai Medical University, Shanghai 200032, China.
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%). By pharmacological test, droloxifene citrate shows two new bioactivities: (1) obvious effect on reversing the MDR of K562/A02 cells and modulating mdrl, GST pi and TopoII alpha 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.