title: Inhibitory and Activating Effects of Some Flavonoid Derivatives on Human Pyruvate Kinase Isoenzyme M2.
abstract: 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.
authors.affiliation: Department of Chemistry, Faculty of Science, Cankiri Karatekin University, Cankiri, Turkey.
authors.forename: Sevki
authors.initials: S
authors.lastname: Adem
authors.affiliation: Faculty of Engineering, Giresun University, Giresun, Turkey.
authors.forename: Abdulselam
authors.initials: A
authors.lastname: Aslan
authors.affiliation: Institute for Biological Interfaces (IBG-1), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen, Germany.|Department of Organic Chemistry, University of Paderborn, Paderborn, Germany.
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Ahmed
authors.affiliation: Department of Organic Chemistry, University of Paderborn, Paderborn, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Krohn
authors.affiliation: Department of Chemistry, Faculty of Science, Cankiri Karatekin University, Cankiri, Turkey.
authors.forename: Caglar
authors.initials: C
authors.lastname: Guler
authors.affiliation: Faculty of Pharmacy, Agrı Ibrahim Cecen University, Agri, Turkey.
authors.forename: Veysel
authors.initials: V
authors.lastname: Comaklı
authors.affiliation: Faculty of Pharmacy, Agrı Ibrahim Cecen University, Agri, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Demirdag
authors.affiliation: Faculty of Pharmacy, Agrı Ibrahim Cecen University, Agri, Turkey.
authors.forename: Muslum
authors.initials: M
authors.lastname: Kuzu
mesh_terms: D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids; D011770:Pyruvate Kinase
keywords: Cancer; Enzyme activation; Enzyme inhibition; Flavonoid derivatives; Pyruvate kinase isoenzyme M2