Pyruvate kinase isoenzyme M2 (PKM2) is one of the most important control point enzyme in glycolysis pathway. Hence, its inhibitors and activators are currently considered as the potential anticancer agents. The effect of 28 polyphenolic compounds on the enzyme activity was investigated in vitro. Among these compounds, neoeriocitrin, (-)-catechin gallate, fisetin, (±)-taxifolin and (-)-epicatechin have the highest inhibition effect with IC50 value within 0.65-1.33 µM range. Myricetin and quercetin 3-β-D-glucoside exhibited the highest activation effect with 0.51 and 1.34 µM AC50 values, respectively. Twelve of the compounds showed inhibition effect within 7-38 µM range of IC50 value. Sinapinic acid and p-coumaric acid showed an activation effect with 26.2 and 22.2 µM AC50 values, respectively. The results propose that the polyphenolics may be the potential PKM2 inhibitors/activators, and they may be used as lead compounds for the synthesis of new inhibitors or activators of this enzyme.

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In this research, a new series of ( E) -3-(4-substitutedphenyl)-1-(4'-morpholinophenyl)prop-2-en-1-one derivatives 1-7 was synthesized, aiming to develop effective antiproliferative agents. The antiproliferative activities of compounds 1-7 were examined against HeLa and C6 cell lines at eight different concentrations using the BrdU ELISA assay.The activity results were compared with reference anticancer drug 5-fluorouracil (5-FU). Compound 1 had almost the same antiproliferative activity as 5-FU. Compounds 1-7 were found to have greater effects against the C6 cell line than the HeLa cell line. These compounds were also tested in order to determine their effects on enzyme activities. Compounds 2 and 3 exhibited strong activator characteristics against pyruvate kinase isoenzyme M2 (PKM2) with AC 50 values of 2.2 and 14.28 µ M. Compounds 2, 3, and 7 acted as inhibitors with IC 50 values in the range of 84.08-165.38 µ M for carbonic anhydrase isoenzyme I (hCA I), and compounds 3 and 4 demonstrated inhibitory effects against carbonic anhydrase isoenzyme II (hCA II) with IC 50 values of 108.11 and 112.52 µ M, respectively. hCA II was activated by derivatives 1, 2, 6, and 7 with AC 50 values in the range of 85.53-146.59 µ M.

Pyruvate kinase isoenzyme M2 (PKM2) is expressed excessively in many different cancer types and it plays an important role in the control of glucose metabolism. Thus, it is evaluated as an important target in the development of medication for cancer. The flavonoids comprise a large group of natural products with variable phenolic structures and occur mainly in plants. They are of great interest due to their biological properties. In this study, the effects of various flavonoid derivatives on the PKM2 enzyme activity were analyzed in vitro. The flavonoid derivatives 1 and 2 showed inhibition effect with IC50 values of <60 μM. IC50 values of compounds 3-8 were calculated as 134, 415, 145, 163, 295 μM, and 3.5 mM, respectively. The molecules 9-12 showed an activation effect with values of AC50 of less than 90 μM. The IC50 values of the derivatives 13-17 were calculated as 115, 150, 200, 221, and 275 μM, respectively. The results show that catechin derivatives can be probably used as lead compounds for the design of PKM2 enzyme activators and inhibitors.

Iron is an indispensable element for vital activities in almost all living organisms. It is also a cofactor for many proteins, enzymes, and other essential complex biochemical processes. Therefore, iron trafficking is firmly regulated by Hepcidin (Hamp), which is regarded as the marker for iron accumulation. The disruption of iron homeostasis leads to oxidative stress that causes various human diseases, but this mechanism is still unclear. The aim of this study is to provide a better in vivo and in vitro understanding of how long‐term iron overload affects the gene expression and activities of some antioxidant enzymes, such as glucose 6‐phosphate dehydrogenase (G6PD), 6‐phosphogluconate dehydrogenase (6PGD), and glutathione reductase (GR) in the spleen. The findings of this study show that iron overload reduces the gene expression of G6pd, 6pgd, and Gr, but its actual effect was on the protein level.