Inhibice lidského rekombinantního CYP2D6 isochinolinovými alkaloidy

The purpose of this work was to screen a set of isoquinoline alkaloids for their inhibitory potency toward CYP450 isoenzyme CYP2D6. Since the human cytochrome P450 plays a pivotal role in a metabolism of both xenobiotics and endogenous substances, studying its interactions is a basic task in early drug development. CYP2D6 is due to its high polymorphism monitored very often. The in vitro method with fluorometric detection was used to determine the inhibitory effect of 20 alkaloids towards the recombinant human CYP2D6. Isoquinoline alkaloids were divided into the groups based on their relative structures. It was determined that 11 out of 20 are potent inhibitors, 3 moderate, 5 weak and one is not inhibitor. In percentage representation it means that 70% of all measured compounds are at least moderate potent inhibitors to CYP2D6 in this assay. They create mainly the members of protoberberine alkaloid group. The structure of these compounds might contribute to the searching of new inhibitors for data-sets for in silico drug metabolism predicting methods.