Figure 1.

Chemical structures and P-gp modulating activities of different generations of synthetic flavonoids. Three generations of synthetic dimeric flavonoids were designed and synthesized to reverse P-gp-mediated MDR. EC₅₀ was the effective concentration of a modulator at which the IC₅₀ of an anticancer drug can be reduced by half in the cancer cell line. RF (relative-fold) was the ratio of EC₅₀ of apigenin to EC₅₀ of different synthetic flavonoids. ^a Structure and EC₅₀ of apigenin and 9d had been reported in 2006 [21]. ^b Structure and EC₅₀ of 61 had been reported in 2009 (Reprinted/adapted with permission from ref. [22], copyright © 2009 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. ^c Structure and EC₅₀ of FD18 had been reported in 2012 [23].