Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium 
homeostasis and its impairment results in pathologies such as myopathy, heart 
failure or diabetes. Modulation of SERCA activity may represent an approach to 
the therapy of diseases with SERCA impairment involvment. Quercetin is flavonoid 
known to modulate SERCA activity. We examined the effect of nine novel quercetin 
derivatives on the activity of the pump. We found that 
5-morpholinohydroxypoxyquercetin, di(prenylferuoyl)quercetin, 
di(diacetylcaffeoyl)-mono-(monoacetylcaffeoyl)quercetin and 
monoacetylferuloylquercetin stimulated the activity of SERCA. On the contrary, 
monochloropivaloylquercetin, tri(chloropivaloyl)quercetin, pentaacetylquercetin, 
tri(trimethylgalloyl)quercetin and diquercetin inhibited the activity of the 
pump. To identify compounds with a potential to protect SERCA against free 
radicals, we assessed the free radical scavenging activity of quercetin 
derivatives. We also related lipophilicity, an index of the ability to 
incorporate into the membrane of sarcoplasmic reticulum, to the modulatury 
effect of quercetin derivatives on SERCA activity. In addition to its ability to 
stimulate SERCA, di(prenylferuloyl)quercetin showed excellent radical scavenging 
activity.