Abstract: P-glycoprotein(P-gp)-mediated drug efflux from cells is believed to be an important mechanism in multidrug resistance(MDR)in cancer chemotherapy. Isoflavone derivatives may selectively antagonize P-gp in MDR cancer cells. Twenty-nine daidzein and genistein derivatives containing a basic chain at 7, 8, and 4′-position were synthesized and evaluated for their MDR reversal activity in vitro. MTT assay showed that most of the target compounds exhibited MDR reversal activity on human chronic myeloid leukemia cell line K562/A02 at different levels and compound 8b showed potent MDR reversal activity with the reversal fold(RF)value of 3. 74. The 2D-QSAR study was performed via MOE 2009 software with a training set of thirty-two isoflavone derivatives united from our previous work. The model yielded good results including high conventional correlation(r2)coefficients(0. 821)and cross-validated(q2)coefficients(0. 692)which are helpful for further structural optimizations of isoflavone derivatives for MDR reversal activity.