In vitro effects of some flavones on human pyruvate kinase isoenzyme M2.
PKM2 is an important target for designing anticancer drug. Inhibitors and activators of this enzyme are suitable molecules for use in treating cancer. The aim of the present study was to investigate the effect of certain flavones on PKM2. Apigenin, wogonin, flavone, 3-hydroxyflavone, 5-hydroxyflavone, 6-hydroxyflavone, and 7-hydroxyflavone effectively inhibited PKM2, with IC50 in the range of 0.99-2.120 μM. The kinetic study indicated that these compounds acted as noncompetitive with Ki values of 3.53-5.67 μM toward phosphoenolpyruvate. Scutellarin and tangeritin demonstrated strong activation effect with AC50 values < 2 μM. Diosmetin, baicalin, baicalein, and luteolin showed an intermediate-level activator effect. These results demonstrate that flavone and their analogs could serve as leading compounds to develop new potent and selective inhibitor and activator for PKM2.
Chemistry Department, Faculty of Science, Cankiri Karatekin University, Cankiri, Turkey. sevkiadem@gmail.com.
Erdem
E
Aslan
Sevki
S
Adem
D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology; D047309:Flavones / Q000494:pharmacology*; D005965:Glucuronates / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D044950:Flavanones; D047309:Flavones; D005965:Glucuronates; D007527:Isoenzymes; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins
Cancer; PKM2; activation; flavone; inhibition