ABSTRACT
Based on the structure of three previously established lead compounds, fifteen selected chalcones were synthesized and evaluated for their multidrug resistance (MDR) reversal activity on mouse lymphoma cells. The most active chalcones were stronger revertants than the positive control, verapamil. In the model of combination chemotherapy, the interactions between the anticancer drug doxorubicin and two of the most effective compounds were measured in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction for one of these compounds was indifferent while that for the other one was additive. Furthermore, two chalcones inhibited 50% of cell proliferation in concentration of around 0.4 µg/mL and were from 2- to 100-fold more active than the most chalcones. The structure-activity relationships were obtained and discussed in view of their usefulness for the design of chalcone-like P-gp modulators and drugs able to treat resistant cancers.
