Objective: In this study, the synthesis of a series of derivatives had been carried out by
bioisosterism design on the basis of dimethyl cardamonin (DMC). Subsequently, we evaluated their
reversal activities as potential P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) agents.
Methods: Dimethyl cardamonin derivatives were synthesized from acetophenones and the
corresponding benzaldehydes in the presence of 40% KOH by Claisen-Schmidt reaction. And their
cytotoxicity and reversal activities in vitro were assessed with MTT. Moreover, the compound B4 were
evaluated by doxorubicin (DOX) accumulation, Western blot and wound-healing assays deeply.
Results: The results showed that compounds B2, B4 and B6 had potency of MDR reversers with little
intrinsic cytotoxicity. Meanwhile, these compounds also demonstrated the capability to inhibit MCF-7
and MCF-7/DOX cells migration. Besides, the most compound B4 was selected for further study, which
promoted the accumulation of DOX in MCF-7/DOX cells and inhibited the expression of P-gp at protein
Conclusion: The above findings may provide new insights for the research and development of
P-gp-mediated MDR reversal agents.