Development of nordihydroguaiaretic acid derivatives as potential multidrug-resistant selective agents for cancer treatment

Abstract

In this research, we designed and synthesized a new series of nordihydroguaiaretic acid (NDGA) derivatives for multidrug resistance (MDR) research. A methylsulfonyl NDGA derivative, ((2R,3S)-2,3-dimethylbutane-1,4-diyl)bis(benzene-4,1,2-triyl) tetramethanesulfonate (5d), was found to inhibit MDR1 gene expression and suppress drug resistant MES-SA/Dx5 cells. Moreover, the combination of 5d and doxorubicin/terameprocol (M₄N) showed a profound synergistic effect on inhibition of drug resistant cancer cells, suggesting that 5d is a potential adjuvant applied with doxorubicin or terameprocol in cancer treatment.