Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the
success of chemotherapy in cancer treatment. The development of new drug candidates which may
serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of
natural products, such as flavonoids, offer an interesting motif from the perspective of drug design.
Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone
core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional
group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic
adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity
of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the
rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned
efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than
the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an
interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the
therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer
treatment, since they exhibited the P-gp efflux pump modulating activity
